Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MOPP (mechlorethamine, vincristine, procarbazine, prednisone) was the first successful regimen for the treatment of Hodgkin's disease. It has the longest period of follow-up and is best studied as to its benefits and acute and long-term side effects. The acute toxicity of the side effects, including nausea and/or vomiting, hair loss, and myelosuppression, may have been reason to modify doses of nitrogen mustard, an agent whose dose intensity may be critical in achieving long-term benefits. The substitution of chlorambucil and vinblastine in the ChlVPP (chlorambucil, vinblastine, procarbazine, prednisone) program has relieved all of these acute toxicities, except myelosuppression. The long-term toxicity of sterility, especially in males, and myelodysplasia is most likely due to alkylating-agent toxicity and would not be influenced by the various MOPP variants, such as MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), ChlVPP, and COPP (chlorambucil-vincristine, procarbazine, prednisone). Doxorubicin-containing regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and ABDIC (doxorubicin, bleomycin, dacarbazine, lomustine, prednisone), have been second-line treatments that have significant antitumor effect and, as such, have resulted in few, if any, long-term cures in most series. ABVD has been incorporated into alternating MOPP/ABVD schemes or in hybrids that attempt to offer all active agents, such as MOPP/ABV. The initial experience has been encouraging with high and durable complete remissions (CRs). MOPP/ABVD x 12(1) and MOPP-2/ABVD-2(2) have been compared with MOPP alone with a significant superiority for the alternating regimens. Other randomized trials have not shown any superiority for the alternating program. The Cancer and Leukemia Group B (CALGB) has compared MOPP with MOPP/ABVD given with a third arm of ABVD alone. The complete response and time-to-treatment failure rates for MOPP/ABVD and ABVD alone were superior to those for MOPP. Significant modifications of MOPP doses may explain the differences, since only 20% of patients were receiving full doses of nitrogen mustard by the sixth dose. ABVD has unique toxicity, and myelodysplasia and sterility are not seen. Pulmonary fibrosis with radiation and bleomycin is unique to ABVD, as shown in the ABVD experience at the NCl (Milan). Can ABVD be improved? The demonstrated single-dose activity of etoposide in Hodgkin's disease has prompted its inclusion in second-line programs, such as EVA (etoposide, vincristine or vinblastine, doxorubicin). The second-line response rates in the St Bartholomew's (London, England) series (where vincristine was used) was 11 of 19 patients (58%);3 in the ongoing CALGB trial of EVA (vinblastine combination), the response rate is 67%. (ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Can MOPP be replaced in the treatment of advanced Hodgkin's disease? 168 9

Thirty-eight patients with advanced Hodgkin disease were treated with a combination of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) from 1970 to 1973 and followed prospectively. Long-term results after a median follow-up of 14 years are reported. Seventeen of the 28 complete responders (61%) survived more than 10 years from the initiation of chemotherapy. At the current time, 12 of the 28 patients (43%) are continuously disease-free 12.8 to 15.3 years after completing induction chemotherapy. Two additional patients are alive in third and fifth remissions. All relapses occurred within 5.5 years of completing induction chemotherapy. Late complications included sterility, aseptic osteonecrosis, severe pulmonary fibrosis, and chronic uveitis. Four of the complete responders (14%) developed second neoplasms, including acute myelogenous leukemia, non-Hodgkin lymphoma and small cell carcinoma of the lung. All second malignancies were fatal and developed 5-13 years after initiation of induction chemotherapy. Our data confirm that cure is possible with alternative regimens to MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone).
 ...
PMID:Chemotherapy with cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) for Hodgkin disease: fourteen-year follow-up results. 341 72

Pulmonary fibrosis is a serious side effect that limits the therapeutic utility of bleomycin (BLM). Recently, it has been demonstrated that L-3, 4-dehydroproline (DHP), a proline analog, significantly reduced the extent of pulmonary fibrosis in rats administered BLM intratracheally. The present studies were performed to determine the effect of DHP on the oncolytic and toxicologic effects of BLM. DHP (25 mg/kg/day) administered sc concomitantly with BLM (4 mg/kg/day) for 9 consecutive days following a sc inoculation of B16 melanoma cells in BDF1 had no effect on tumor growth inhibition by BLM when tumor growth rate was assessed by tumor volume and by tumor weight. To determine the effect of DHP on the toxicity of BLM, DHP (25 mg/kg/day) and BLM (10 mg/kg/day) were administered to Sprague-Dawley rats for 5 consecutive days followed by 2 days of rest and 5 additional days of drug administration. BLM administration produced decreased body weight gain, acute leukocytopenia, delayed elevation in blood nitrogen levels, chronic lung and kidney disease, and alopecia. Animals administered BLM plus DHP had a similar toxicologic profile. One striking difference was that no animal administered BLM plus DHP developed alopecia, whereas five of eight rats administered BLM alone displayed this untoward effect. These results suggest that DHP neither diminishes the oncolytic activity nor exacerbates the nonpulmonary toxicity of BLM, DHP would appear, therefore, to be a potential candidate as an antifibrotic adjunct to BLM therapy.
 ...
PMID:The effect of L-3, 4-dehydroproline on the antitumor activity and toxicity of bleomycin. 619 Feb 66

The toxicity of the weed-killer paraquat is related to the formation of superoxyde radicals responsible of a progressive and usually lethal pulmonary fibrosis. Recognition of lipid peroxidation of membrane bilayers by free radicals as the causative factor pointed to oxygen as an important cofactor in the severity of paraquat poisoning. It has been shown that any FiO2 over 21% accelerates this process and increases the the mortality of rats and humans. FiO2 21% gave a significant reduction of mortality in rats (DOUZE 1976). We proposed this therapy (1978-1879) in 6 cases of paraquat poisoning. It was conducted with induction of a barbiturate coma, hypothermia, curarisation and hypo-oxygenation (FiO2 around 14% thanks to the adjunction of nitrogen to assisted ventilation). In 5/6 patients, these technics did not prevent the evolution towards death. This evolution was in fact predicted, according the following prognostic factors: suicide, more than a mouthful ingestion, oesophago-gastric burns detected by endoscopy, organic renal failure, high plasma paraquat level. Associated methods of elimination (Fuller's earth, provoked diarrhea, furosemide, hemoperfusion and hemodialysis) did not change the early established prognosis. The only survival was observed in an accidental poisoning with undetectable plasma paraquat and isolated oral burns: the herbicide had been probably spit out. This survival cannot be related to hypo-oxygenation. This failure is not definitive, according to us: this therapy should be undertaken only after minimal, accidental poisoning possibly evolving to pulmonary fibrosis. It appears unuseful in massive, suicidal poisonings, leading readily to a lethal circulatory failure.
 ...
PMID:[Hypo-oxygenation in paraquat poisoning. Apropos of 6 cases]. 661 25

Geometric analysis of the chest roentgenogram allows calculation of estimated gas volume. If roentgenograms are made on individual patients or in epidemiologic studies in which relatively expensive nitrogen meters or body plethysmographs are not available, the thoracic roentgenogram provides an economical alternative. This study compares two roentgenographic methods of estimating total lung capacity in 154 subjects who also had total lung capacity estimated by the 7-minute nitrogen-washout technique or by total-body plethysmography. Results with the roentgenographic techniques were closely comparable with each other and with those of the gas-dilution and total-body plethysmograph methods in normal subjects. The planimetric method consistently estimated higher total lung capacity than the elliptic method in men and women with total lung capacity of 7.75 liters or less. In patients with severe obstructive lung disease, the roentgenographic methods were more closely comparable with body plethysmography, which is believed to be the most accurate, whereas the nitrogen-rinsing and similar gas-dilutional methods tended to underestimate the true volumes. The roentgenographic techniques also proved to be reliable in a small group of patients with varying degrees of pulmonary fibrosis.
 ...
PMID:Roentgenologic determination of total lung capacity. 744 23

In the present paper, we have reviewed experimental animal studies on the effects of the two most important oxidant airborne pollutants, nitrogen dioxide and ozone, on the respiratory system. The toxic effects depend on concentration and length of exposure, and are generally similar for both oxidants, with ozone operative at lower concentrations. High doses of both oxidants cause death due to lung oedema. Exposure to sublethal levels causes functional alterations such as airflow limitation and airway hyperresponsiveness to bronchoconstrictor stimuli. These effects, which are generally reversible, are associated with epithelial injury, oedema and airway and parenchymal infiltration by inflammatory cells. Loss of cilia of airway epithelium and necrosis of type I alveolar epithelial cells are the most prominent consequences at the epithelial level. Inflammation is characterized by early neutrophilic infiltration, followed by an increased number of mononuclear cells, predominantly alveolar macrophages. After long-term exposure, whilst nitrogen dioxide causes predominantly emphysema, ozone produces mainly pulmonary fibrosis. Biochemical effects include lipid peroxidation, increased antioxidant metabolism, and alteration of enzyme activity. Nitrogen dioxide and ozone may also alter the immunological response and reduce the defence against infections, increasing the susceptibility of exposed animals to infections.
 ...
PMID:Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research. 748 4

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.
 ...
PMID:A new model of progressive pulmonary fibrosis in rats. 834 14

To evaluate the contribution of reactive nitrogen species to inflammation by asbestos, Fischer 344 rats were exposed to crocidolite or chrysotile asbestos by inhalation to determine whether increases occurred in nitric oxide (NO.) metabolites from alveolar macrophages (AMs). AMs from animals inhaling asbestos showed significant elevations (p < .05) in nitrite/nitrate levels which were ameliorated by NG-monomethyl-L-arginine (NMMA), an inhibitor of inducible nitric oxide synthase (iNOS) activity. Temporal patterns of NO. generation from AMs correlated with neutrophil influx in bronchoalveolar lavage samples after asbestos inhalation or bleomycin instillation, another model of pulmonary fibrosis. To determine the molecular mechanisms and specificity of iNOS promoter activation by asbestos, RAW 264.7 cells, a murine macrophage-like line, and AMs isolated from control rats were exposed to crocidolite asbestos in vitro. These cells showed increases in steady-state levels of iNOS mRNA in response to asbestos and more dramatic increases in both iNOS mRNA and immunoreactive protein after addition of lipopolysaccharide (LPS). After transfection of an iNOS promoter/luciferase reporter construct, RAW 264.7 cells exposed to LPS, crocidolite asbestos and its nonfibrous analog, riebeckite, revealed increases in luciferase activity whereas cristobalite silica had no effects. Studies suggest that NO. generation may be important in cell injury and inflammation by asbestos.
 ...
PMID:Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models. 958 8

Sprague-Dawley rats were exposed to 0.8 ppm ozone (O3), to 14.4 ppm nitrogen dioxide (NO2), or to both gases simultaneously for 6 h per day for up to 90 d. The extent of histopathologic changes within the central acinus of the lungs was compared after 7 or 78 to 90 d of exposure using morphometric analysis by placement of concentric arcs radiating outward from a single reference point at the level of the bronchiole- alveolar duct junction. Lesions in the lungs of rats exposed to the mixture of gases extended approximately twice as far into the acinus as in those exposed to each individual gas. The extent of tissue involvement was the same at 78 to 90 d as noted at 7 d in all exposure groups. At the end of exposure, in situ hybridization for procollagen types I and III demonstrated high levels of messenger RNA within central acini in the lungs of animals exposed to the combination of O3 and NO2. In contrast, animals exposed to each individual gas had a similar pattern of message expression compared with that seen in control animals, although centriacinar histologic changes were still significantly different from control animals. We conclude that the progressive pulmonary fibrosis that occurs in rats exposed to the combination of O3 and NO2 is due to sustained, elevated expression of the genes for procollagen types I and III. This effect at the gene level is correlated with the more severe histologic lesions seen in animals exposed to both O3 and NO2 compared with those exposed to each individual gas. In contrast, the sustained expression of the procollagen genes is not associated with a shift in the distribution of the lesions because the area of change in each group after 7 d of exposure was the same as after 78 to 90 d of exposure.
 ...
PMID:Centriacinar remodeling and sustained procollagen gene expression after exposure to ozone and nitrogen dioxide. 992 22

Tumor necrosis factor a (TNFalpha) and manganese superoxide dismutase (MnSOD) are thought to play critical roles in the process of lung injury, repair, and disease. The induction of TNFalpha and MnSOD were examined in a model of progressive pulmonary fibrosis along the length of the alveolar duct in rats exposed for 1, 5, and 8 weeks to a combination of 0.8 ppm ozone and 14.4 ppm nitrogen dioxide. This oxidant injury model results in a triphasic response with an initial inflammatory stage during weeks 1-3, followed by a partial resolution at weeks 4-5, and a final stage of rapidly progressive fibrosis during weeks 6-8. Changes in TNFalpha and MnSOD labeling for the proximal and distal alveolar ducts of the lungs were quantified using immunohistochemistry and morphometric techniques at 1, 5, and 8 weeks of exposure. A significant elevation in MnSOD was noted in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following 8 weeks of exposure. Labeling for TNFalpha only in the proximal region of the alveolar duct, was significantly increased in alveolar macrophages after 1 and 8 weeks of exposure, while a significant increase in TNFalpha labeling of interstitial cells in proximal regions was noted at all time points. We conclude that MnSOD is elevated in areas of focal injury as well as the more distal protected areas of the lungs, while TNFalpha correlates strongly with both the temporal and spatial aspects of greatest cellular injury in the lungs.
 ...
PMID:Quantitation and localization of pulmonary manganese superoxide dismutase and tumor necrosis factor alpha following exposure to ozone and nitrogen dioxide. 1077 28


1 2 3 Next >>