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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A guinea pig model of immunosuppression was utilized to study the effects of immunosuppressive chemotherapy on lung response to challenge with Pseudomonas aeruginosa. Study groups included normal guinea pigs, as well as guinea pigs that received a one-week course of cortisone acetate (CA, 100 mg/kg per day) plus 15 mg of cyclophosphamide (CTX)/kg per day (CA + LoCTX group) or 30 mg of cyclophosphamide/kg per day (CA + HiCTX group). Separate groups received CA or HiCTX alone. Intratracheal instillation of P. aeruginosa resulted in bilateral hemorrhagic pneumonia in both normal and immunosuppressed animals. Survival was 100% for normal animals and for those given CA alone, 67% in the CA + LoCTX and the HiCTX groups, and 0 in the CA + HiCTX group. Increased mortality correlated with a diminished polymorphonuclear leukocyte inflammatory response in infected lung tissues and also with the addition of CA to CTX. Clearance of viable P. aeruginosa from lung tissue was significantly reduced in animals receiving the combination CA + HiCTX. Thus, decreased lung inflammation and the addition of CA appeared to be important determinants for fatal pseudomonas pneumonia.
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PMID:Pathogenesis of Pseudomonas aeruginosa pneumonia during immunosuppression. 9 88

One single injection of 50 mg/kg live weight cyclophosphamide or more to calves was followed by a latency of few days after which pneumonia or enteritis developed and caused death within one or two weeks. Cyclophosphamide application led to pronounced changes in the white blood count characterised, at the beginning, by rise of neutrophilic granulocytes and decline of lymphocates. Primary rise of granulocytes then was followed by almost complete disappearance of them. In those calves that survived the parameters of the white blood count were not restoredto normal until several weeks had elapsed. While an injection of 30 mg/kgcyclophosphamide usually was tolerated without any visible clinical reaction, it was also accompanied by the above pronounced changes in the white blood count. The activity of the reticulohistiocytary system, as recordable by means of ink and bacterial clearance, was not markedly affected by one single injection of 30mg/kg or 40 mg/kg cyclophosphamide. Calves with cyclophosphamide treatment exhibited unambigous humoral immune response, yet somewhat delayed or reduced in comparison to controls. While one single intravenous injectionof 30 mg/kg cyclophosphamide alone failed to trigger any clinical disease, it proved to be capable of rendering calves more susceptible to pneumonia pathogens. It, therefore, might be suitable for supporting experimental infection and thus facilitating the study of enzootic pneumonia of calf which usually is difficult to reproduce.
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PMID:[The reaction of calves to parenteral administration of cyclopheosphamide]. 84 5

Irradiation of the mouse right or left hemithorax at 14 or 18 Gy produced a dose-dependent rise in breathing rate 16 weeks after irradiation without significant mortality. The measurement of breathing rate changes following right hemithoracic irradiation combined with the maximally tolerated dose of cytotoxic drugs was assessed as a method for qualitatively detecting drug-irradiation interactions which either exacerbate pneumonitis or alter its time course. Cyclophosphamide at 100 mg/kg accentuated and accelerated the rise in breathing rate, culminating in early mortality. BCNU 30 mg/kg delayed the appearance of the radiation response. Busulphan 30 mg/kg appeared to be radioprotective, but this was shown to be due to the DMSO-containing vehicle. Doxorubicin 6 mg/kg had no effect when combined with right or left hemithoracic irradiation. Carboplatin 100 mg/kg, vindesine 4 mg/kg and vinblastine 4 mg/kg had no substantial effect upon the changes in breathing rate.
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PMID:Mouse hemithoracic irradiation and its interaction with cytotoxic drugs. 141 May 72

In the prior two reports, we demonstrated that G-CSF induced the polarization of neutrophils by itself, and also enhanced superoxide production from neutrophils stimulated by the chemotactic peptides. In this study, we have examined the protective effect of G-CSF in vivo on Pseudomonas pneumonia and septicemia in mice. Cyclophosphamide (CY) induced severe reduction of the number of peripheral leukocytes and weakened resistance for Psuedomonas aeruguinosa infection of mice. However, in mice receiving recombinant human G-CSF four daily subcutaneous injection, the number of leukocytes, particulary neutrophils, increased more rapidly than in controls receiving saline. Moreover G-CSF enhanced a protective effect to pulmonary and systemic pseudomonas infections. When G-CSF was administered together with antibiotics, significant synergism in the protection against pulmonary infection of Pseudomonas was observed. Carrageenan treatment decreased the protective effect of G-CSF. These results suggested that the protective effect of G-CSF against P. aeruginosa infection depends not only on PMN but also another complexed host defence mechanism.
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PMID:[Studies on defence effects of recombinant human granulocyte colony-stimulating factor (G-CSF) to infections. III. Protective effect on pulmonary and systemic infections of P. aeruginosa in neutropenic mice]. 169 96

Preparative regimens for bone marrow transplantation (BMT) use a sequence of drugs, such as cyclophosphamide, in combination with radiation. However, the optimum sequencing of the two agents that will maximize tumor cell kill and minimize normal tissue damage is unknown and controversial. The studies presented here were done in order to determine the effect of cyclophosphamide on bone marrow and lung damage in mice when given 24 h before or after total body irradiation (TBI). A range of single doses of TBI was given before or after a single sublethal dose of 180 mg/kg of cyclophosphamide. The bone marrow of all mice intended for lung damage assessment was reconstituted with 5 x 10(6) syngeneic bone marrow cells. Lung damage was assessed by breathing rate and lethality; bone marrow damage by lethality at 30 days. LD50 values for pneumonitis were obtained between 30 and 84 days after cyclophosphamide and radiation and between 80 and 180 days after radiation alone. Dose modifying factors were obtained as the ratio of LD50s for mice given only TBI compared to those for mice given cyclophosphamide and TBI. Cyclophosphamide enhanced radiation pneumonitis when given before or after TBI, giving DMFs of 1.4 and 1.2 (1.1-1.4, 95% c.l.) respectively. The effect of cyclophosphamide on radiation pneumonitis was drug dose-dependent. The LD50 for death from bone marrow damage was reduced when cyclophosphamide was given either before or after TBI but the effect was greater, i.e. the LD50 was lower when cyclophosphamide was given after TBI. These data show that cyclophosphamide given 24 h after TBI causes less lung damage but more bone marrow damage in this mouse model.
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PMID:Cyclophosphamide 24 hours before or after total body irradiation: effects on lung and bone marrow. 192 49

The purpose of these studies was to quantify the effects of radiation given to mouse lungs at intervals up to 6 months after injection of the maximally tolerated dose of cyclophosphamide. In one set of experiments a single i.p. injection of 300 mg/kg of cyclophosphamide was followed at either 1, 3, or 6 months by a range of single doses of gamma-rays delivered to the whole thorax only. In a second set of experiments mice were given five daily i.p. injections of cyclophosphamide, 100 mg/kg, followed at 1, 3, and 6 months by a range of fractionated doses of X-rays. Breathing rate, histology, and mortality were used to assess lung damage. These data were compared with age-matched animals given either the drug alone or single doses of radiation alone. Dose-response curves of lethality were constructed and fitted by a logit program, and 50% lethal doses with 95% confidence limits were determined at monthly intervals after irradiation. Dose enhancement factors were then calculated at this isoeffect for the mice given the drug and radiation. Deaths from radiation pneumonitis occurred as early as 6 weeks in mice given cyclophosphamide before irradiation; few deaths occurred after 26 weeks. However, in the mice given radiation alone, deaths from pneumonitis did not occur before 12 weeks. Cyclophosphamide given as either single doses or fractionated doses at all three times before irradiation enhanced radiation pneumonitis in mouse lung. Dose enhancement factors of 1.2, 1.4, and 1.3 were obtained when single doses of radiation followed single doses of cyclophosphamide at 1, 3, and 6 months, respectively. The dose enhancement factor for radiation pneumonitis after the fractionated exposures was less, 1.1, and was independent of time between the two treatments. An enhancement factor of 1.2 was observed for the later wave of lung damage in those few studies available for analysis at this time. These data clearly show that prior treatment of the animal with cyclophosphamide significantly reduces the radiation dose that can be given to the lung for as long as 6 months after drug treatment. In addition, lung damage occurred sooner when the drug was given prior to irradiation. These data indicate that the lung will be sensitive to retreatment with radiation when a full tolerance dose of cyclophosphamide precedes radiation.
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PMID:Residual damage in mouse lungs at long intervals after cyclophosphamide treatment. 231 5

Between June 1973 and February 1979, 409 patients with inoperable advanced non-oat cell carcinoma of the lung were randomized on RTOG protocol 73-02. Three treatment arms were evaluated: 40 Gy split course, 30 Gy continuous course, and 40 Gy continuous course. Patients were also randomized to receive cytoxan or no further therapy following irradiation. Three hundred sixteen patients were evaluable. Palliation of symptoms was achieved in 60% with 1/4 of the patients becoming symptom-free. Complete regression of local and regional tumor was produced in 15% and partial regression in 26%. There is no significant difference between the treatment arms in these objective response rates. Median survival times were approximately 6 months. No significant benefit was demonstrated by the adjuvant use of Cytoxan. Although the number of complete responses produced was relatively small, patients achieving a complete response had a significantly longer median survival than the remaining patients, i.e., 14.5 months versus 6 months. Significant toxicity occurred in fewer than 6% of patients. Radiation pneumonitis counted for the majority of these adverse reactions. Toxicity occurred somewhat more often in the group treated with 40 Gy split course therapy. Implications for further studies are discussed.
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PMID:Palliative radiotherapy for inoperable carcinoma of the lung: final report of a RTOG multi-institutional trial. 257 38

Cyclophosphamide is an alkylating agent with a wide spectrum of activity against malignant tumours. Because of its pronounced immunosuppressive effect it is also frequently used in organ transplantations and in the treatment of certain autoimmune diseases. The drug has toxic side effects, however, some of which are ascribed to specific metabolites. This report describes a patient who developed cyclophosphamide associated cystitis and pneumonitis while being treated for Wegener's granulomatosis. Early recognition of the condition and discontinuation of therapy is essential for a favourable outcome.
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PMID:[Cyclophosphamide-induced pneumonitis]. 270 79

Thirty-nine previously untreated small cell lung cancer patients received cyclophosphamide (CTX) + adriamycin (ADM) + vincristine (VCR) (CAV). The doses initially used were CTX 1,000 mg/body day 1, ADM 50 mg/body day, VCR 1 mg/body day, 8, 15 or 2 mg/body day(group A). Later, CTX 1,000 mg/m2 day, ADM 60 mg/m2 day, VCR 1.4 mg/m2 day were used. All patients had PS 0-3, 24 had limited disease (LD) and 15, extensive disease (ED). The overall response rate and the complete response (CR) rates were 63% (15/24) and 21% (5/24) for LD, and 21% (3/14) and 0% (0/14) for ED, respectively. The median response durations were 22 weeks for LD and 33 weeks for ED. The median CR duration in LD patients was 23 weeks. Twelve LD and 1 ED patient received thoracic radiotherapy (RT) optionally after 2-4 courses of CAV therapy. Eventually, 8 patients achieved CR. The median survival for LD, ED and all cases were 43 weeks, 37 weeks and 41 weeks, respectively. The 1, 2 and 3-year survival rates were 42, 25 and 21% for LD, and 40, 7 and 0% for ED. Three patients were long-term disease-free survivors (greater than 3 years), and these had LD and received RT. There were 3 chemotherapy-related deaths (2 patients with leukopenia + infection, 1 patient with drug-induced pneumonitis). The survival results of CAV therapy in our hospital were comparable with the recent results of chemotherapies available against small cell lung cancer.
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PMID:[Cyclophosphamide, adriamycin and vincristine (CAV) in the treatment of small cell lung cancer]. 283 19

Seventy patients with poor prognosis, metastatic breast cancer were treated with FUVAC induction chemotherapy (5-fluorouracil, vinblastine, Adriamycin [doxorubicin] and cyclophosphamide). Consolidation therapy was given to 30 of 48 responders (63%), of whom 23 received sequential hemibody irradiation (HBI) at 8 cGy, corrected in the upper half for lung transmission. Seven received high dose cyclophosphamide and total body irradiation (TBI) with subsequent infusion of stored, cryopreserved autologous bone marrow. The response rate to induction therapy was 71% (complete [CR] in 21%). The median survival for all patients entered in this study is 12 months. With consolidation, one CR patient who received cyclophosphamide and TBI is disease free at 20+ months, off all treatment, while HBI did not produce longterm remissions. Of 17 partial response (PR) patients, two of 12 improved to CR with HBI, and one of five improved with cyclophosphamide plus TBI, but all ultimately relapsed. The main toxicity of sequential HBI was myelosuppression, with prolonged thrombocytopenia in 13%; only one case of radiation pneumonitis occurred (3%). Cyclophosphamide and TBI produced temporary, reversible marrow aplasia without other major toxicity. We recommend further investigation of Cytoxan (Bristol Myers Oncology Division, Evansville, IN) and TBI for breast cancer patients in remission after chemotherapy.
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PMID:Combination chemotherapy and systemic irradiation consolidation for poor prognosis breast cancer. 354 30


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