Biomedical subjects

R Breuer

Publications and source records attributed to R Breuer.

At least 19 recordsLinked to original sources

PubMed2001

All-trans-retinoic acid (ATRA) is of no benefit in bleomycin-induced lung injury.

All-trans-retinoic acid (ATRA) has anti-fibrotic and antiinflammatory properties, and may be useful as a therapeutic agent in lung fibrosis. To test this hypothesis we investigated the effect of ATRA on bleomycin-induced lung fibrosis in Sprague-Dawley rats. Treatment groups included: (1) a single intratracheal (i.t.) instillation of bleomycin and daily intraperitoneal (i.p.) injection of 0.5 mg/kg per day ATRA; (2) i.t. bleomycin and i.p. ATRA, 2 mg/kg per day, (3) i.t. bleomycin and i.p. diluent (cottonseed oil); (4) i.t. saline and i.p. ATRA, 0.5 mg/kg per day, (5) i.t. saline and i.p. ATRA, 2 mg/kg per day; and (6) i.t. saline and i.p. diluent. Animals were studied 14 days after i.t. instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semi-quantitative morphological index of lung injury, and by biochemical analysis of lung hydroxyproline content. Overt signs of lung injury were apparent in bleomycin-treated rats by all measures. These changes were not affected by treatment with ATRA at either dose. This study does not support the use of ATRA to prevent or ameliorate lung fibrosis.

Animals↗

PubMed2001

Human recombinant interferon-alpha2a and interferon-alphaA/D have different effects on bleomycin-induced lung injury.

BACKGROUND: Bleomycin (Bleo)-induced lung injury in mice serves as an animal model of pulmonary fibrosis. The pathogenesis of pulmonary fibrosis remains unclear, but it comprises both inflammatory and fibrotic components. The cytokine interferon (IFN)-alpha is produced by macrophages and may modulate both fibrogenesis and the determination of T lymphocyte phenotype in pulmonary fibrosis. OBJECTIVE: To investigate the effect of two preparations of recombinant IFN-alpha (IFN-alphaA/D and IFN-alpha2a) on Bleo-induced lung injury in C57BL/6 mice. METHODS: Mice were treated by a single intratracheal (IT) instillation of 0.06 mg of Bleo in 0.1 ml of saline or saline alone. One of two different IFN-alpha preparations, IFN-alphaA/D or IFN-alpha2a in saline, or saline alone were administered by daily intraperitoneal injections starting 1 day prior to IT instillation. The treatment groups were as follows: IT Bleo and intraperitoneal saline; IT Bleo and intraperitoneal IFN-alpha2a; IT Bleo and intraperitoneal IFN-alphaA/D; IT saline and intraperitoneal IFN-alphaA/D or IFN-alpha2a; IT saline and intraperitoneal saline. The animals were sacrificed 14 days after IT instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage (BAL) fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity and fibrosis fraction and by biochemical analysis of lung hydroxyproline content. RESULTS: In Bleo-treated mice, IFN-alpha2a treatment caused a significant rise in BAL lymphocytes and in cellularity and fibrosis fractions in lung tissue. In contrast, IFN-alphaA/D treatment had no effect on Bleo-induced lung injury. CONCLUSION: IFN-alpha may enhance Bleo-induced lung injury but this effect varies with different IFN preparations.

Animals↗

PubMed2001

Eotaxin-3 but not eotaxin gene expression is upregulated in asthmatics 24 hours after allergen challenge.

Eotaxin is an important mediator of eosinophil recruitment and activation in the airways of asthmatics. Eotaxin-2 and eotaxin-3 are two recently identified chemokines with activity similar to that of eotaxin. Using quantitative polymerase chain reaction analysis, we determined the messenger RNA (mRNA) expression of eotaxin, eotaxin-2, and eotaxin-3 relative to GAPDH mRNA expression in bronchial biopsies and bronchoalveolar lavage fluid (BALF) cells obtained from subjects with mild asthma, asthmatic subjects 24 h after allergen challenge, and normal control subjects. In bronchial biopsies, gene expression was upregulated in asthmatic subjects as compared with control subjects for eotaxin (log median values 3.18 pg/microg, 95% confidence interval [CI]; 2.27 to 3.79 versus 4.37 pg/microg, 95% CI; 3.97 to 4.65, P = 0.003) and for eotaxin-2 (0.82 pg/microg, 95% CI; 0.08 to 1.72 versus 2.97 pg/microg, 95% CI; 1.97 to 3.45, P = 0.006), but no further increase was observed after allergen challenge. In contrast, eotaxin-3 mRNA expression was not increased in asthmatic compared with control subjects, but was dramatically enhanced 24 h after challenge (median log value 1.93 pg/microg, 95% CI; 0.74 to 3.92 versus 4.62 pg/microg, 95% CI; 3.05 to 6.23, P = 0.036). No significant difference between groups was observed in BALF cell gene expression for any of the chemokines examined. These data suggest that eotaxin-3 rather than eotaxin or eotaxin-2 may account for the ongoing eosinophil recruitment to asthmatic airways in the later stages (24 h) following allergen challenge.

Adult↗

PubMed2001

[Contribution of PET using FDG in the diagnosis of lung cancer--first results].

Positron emission tomography (PET), when used with F-18 fluoro-deoxyglucose (FDG), contributes to the evaluation of patients with lung cancer. This technique of imaging detects active tumor tissue by showing increased radiopharmaceutical uptake by metabolically active cells. Thus, PET assists in the early diagnosis of pulmonary malignancies that appear only as non-specific findings on CT-scan or chest X-ray. In addition, it is helpful in staging lung cancer before and after resection, chemotherapy or radiotherapy, or their combined use. We performed 135 FDG-PET studies between July '97-April '99 and present our preliminary results with examples of the main indications for PET in lung cancer.

Adult↗

PubMed2000

The effect of suramin on bleomycin-induced lung injury.

Since transforming growth factor beta (TGF-beta) is presumed to play a role in lung fibrosis, we evaluated the effect of suramin (Sur), a substance with an anti-TGF-beta effect, in vivo on bleomycin (Bleo)-induced pulmonary injury in mice and in vitro on human lung fibroblasts. Four groups of C57BL/6 mice each received one of four treatments: (1) intratracheal (i.t.) instillation of Bleo and intraperitoneal (i.p.) injections of Sur, every other day, starting one day before i.t. instillation of Bleo (Bleo-Sur); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. Sur (Sal-Sur); and (4) i.t. and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage (BAL) fluid, histologically by the semiquantitative morphological index, and biochemically by analysis of lung hydroxyproline content. In vitro, Sur did not affect TGF-beta induced increase of alpha1 (I) collagen mRNA in human lung fibroblasts. In vivo treatment of mice with Sur did not affect Bleo-induced lung injury. These results indicate that despite its potential anti TGF-beta and lymphocytotoxic effects, Sur is not a therapeutic candidate drug for rescue of lung fibrosis.

Animals↗

PubMed2000

Cerebrospinal fluid lactate dehydrogenase isoenzyme analysis for the diagnosis of central nervous system involvement in hematooncologic patients.

BACKGROUND: Central nervous system (CNS) involvement is common in hematooncologic diseases. The aim of the current study was to determine the diagnostic value of cerebrospinal fluid (CSF) lactate dehydrogenase (LDH) isoenzyme analysis for the diagnosis of CNS involvement in hematooncologic patients. METHODS: The study was comprised of 63 consecutive hematooncologic patients without previous CNS disease who underwent CSF examination as an integral part of their initial staging procedures (44 patients) or for the evaluation of neurologic symptoms (19 patients). Fifteen of these patients had CNS involvement by leukemia or lymphoma. The LDH isoenzyme pattern was established in the CSF of all patients and analyzed by the classification and regression trees (CART) method to construct a decision tree for the prediction of CNS involvement. An additional group of 30 consecutive patients comprised a validation set that was used for cross-validation of the CART-derived decision tree. RESULTS: A decision tree, with a single split at LDH5 >/= 2.8% for the prediction of CNS involvement, was constructed and validated by data from a validation set of patients. The decision tree had a sensitivity of 93% and a negative predictive value of 98%. One patient (1.6%) and 2 patients (6.6%) were misclassified in the derivation and validation sets, respectively. Overall, in the combined derivation and validation patient population, the decision tree misclassified 3.2% of patients, whereas CSF cytologic examination misclassified 4.3% of patients. CONCLUSIONS: Analysis of the LDH isoenzyme pattern in CSF fluid may be helpful in the evaluation of CNS involvement in patients with hematologic malignancies. The combination of CSF cytology and LDH isoenzyme analysis may improve the sensitivity of CSF cytology significantly.

Central Nervous System Neoplasms↗

PubMed2000

Gender-specific effects of NAT2 and GSTM1 in bladder cancer.

One approach for risk assessment of cancer is the evaluation of polymorphic enzymes involved in cancer using molecular tools. Phase II enzymes are involved in the detoxification of several drugs, environmental substances and carcinogenic compounds. Here, we analyzed enzymes for their putative relevance in urinary bladder cancer. The hereditable enzyme polymorphism of arylamine N-acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) was studied in 157 hospital-based patients and in 223 control subjects. Slow acetylation was not observed to be a significant risk factor of developing bladder cancer (OR: 1.33; 95% CI 0.85-2.09). One genotype responsible for slow acetylation (NAT2*5B/*6A) was observed significantly more frequently in bladder cancer patients compared with control subjects (OR: 1.63; 95% CI 1.03-2.58). Gender-specific effects were observed when patients were divided into subgroups. In male patients, slow acetylators were identified as carrying a significant increased risk of developing bladder cancer, in particular when the genotype NAT2*5B/*6A was combined with the GSTM1 null genotype (OR: 4.39; 95% CI 1.98-9.74). By contrast, the same genotype combination significantly protected female patients from bladder cancer (OR: 0.21; 95% CI 0.06-0.80).

Adult↗

PubMed2000

Susceptibility genes: GSTM1 and GSTM3 as genetic risk factors in bladder cancer.

Glutathione S-transferase (GST, E.C. 2.5.1.18) comprises a family of isoenzymes that play a key role in the detoxification of such exogenous substrates as xenobiotics, environmental substances, and carcinogenic compounds. At least five mammalian GST gene families have been identified to be polymorphic, and mutations or deletions of these genes contribute to the predisposition for several diseases, including cancer. The gene cluster of GSTM1-GSTM5 has been reported to be localized on chromosome 1p and spans a length of nearly 100 kb. One mutation of the GSTM3 gene generates a recognition site for the transcription factor yin yang 1. As a result of this mutation, the expression of GSTM3 can be influenced. The mutated GSTM3 gene has been reported to be involved in increased susceptibility for the development of cancer, but no information is available concerning its role in bladder cancer. We have identified patients with a heterozygous GSTM3 geno- type who carry a significantly increased risk for the development of bladder cancer. Here we report that the mutation of intron 6 of GSTM3 increases the risk for bladder cancer (odds ratio: 2.31; 95% confidence interval [CI], 1.79-2.82). We developed a procedure to identify heterozygous or homozygous carriers of the GSTM1 alleles. Heterozygous carriers of the GSTM1 null genotype have a significantly elevated risk of developing bladder cancer. We calculated an odds ratio of 3.54 (95% CI, 2.99-4.11) for this genotype. These observations lead to the assumption that the lack of detoxification by glutathione conjugation predispose to bladder cancer when at least one of two alleles is affected. Furthermore, individuals presenting the homozygous wild type of GSTM1 and GSTM3 are significantly protected against bladder cancer.

Aged↗

PubMed2000

The role of BAL in the diagnosis of pulmonary mucormycosis.

Five patients with pulmonary mucormycosis diagnosed during life are described. All had underlying predisposing conditions: either posttransplant or hematologic malignancies. In all cases, the diagnosis was made using fiberoptic bronchoscopy. In three patients, BAL was diagnostic. In two of these patients, the diagnosis was made by identifying the typical hyphae of mucormycosis in the BAL fluid alone. Transbronchial biopsy was diagnostic in three patients. Treatment was based on IV antifungal chemotherapy together with surgical removal of involved lung tissue whenever feasible. The clinical outcome of these patients was dismal and was determined primarily by the underlying condition.

Adult↗

PubMed1999

Lactate dehydrogenase isoenzyme analysis for the diagnosis of pleural effusion in haemato-oncological patients.

This study aimed to evaluate the utility of the pleural fluid lactate dehydrogenase (LDH) isoenzyme algorithm for the differential diagnosis of pleural fluid in patients with haematological malignancies. Twenty consecutive haemato-oncological patients with pleural effusion, hospitalized in the Haematology Department during a 2.75-year period, were prospectively and independently evaluated for the cause of effusion by standard methods for the LDH isoenzyme algorithm. The causes of the pleural effusions established during the standard evaluations were compared to the results obtained from the LDH isoenzyme algorithm. Following the standard evaluation, the pleural effusion was attributed to congestive heart failure in one patient, to infection in six, to the underlying malignancy in 12 and to concomitant congestive heart failure and malignancy in one. LDH isoenzyme analysis correctly predicted the cause of pleural effusion in 18 patients (positive predictive value 90%). In haemato-oncological patients, the pleural fluid LDH isoenzyme pattern may be helpful in the differential diagnosis of the most common causes of pleural effusion.

Biomarkers↗

PubMed1999

The effect of enoxaparin on bleomycin-induced lung injury in mice.

We have evaluated the effect of enoxaparin, a potent antithrombotic drug, on bleomycin (Bleo)-induced pulmonary inflammation in mice. Pulmonary injury was induced by a single intratracheal (i.t.) instillation of Bleo. Four groups of female C57BL/6 mice, each received one of four treatments: (1) i.t. Bleo and daily intraperitoneal (i.p.) injections of enoxaparin (EN) starting one day before i.t. instillation of Bleo (Bleo-EN); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. enoxaparin (Sal-EN); (4) i.t. saline and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage fluid and histologically by an overall semiquantitative index of lung injury and a quantitative image analysis assessing alveolar wall area fraction and fibrosis fraction. Treatment of mice with enoxaparin did not ameliorate Bleo-induced lung injury. Our study does not establish a critical role of procoagulant activity in the evolution of Bleo-induced lung injury and does not support the use of antithrombotic therapy for the prevention of pulmonary fibrosis.

Animals↗

PubMed1999

Effect of immunomodulators on bleomycin-induced lung injury.

BACKGROUND: The role of lymphocytes and their subpopulations in lung fibrosis is as yet unclear. OBJECTIVE: To define the role of immunomodulation in bleomycin-induced inflammatory fibrotic lung injury, by testing the effect of two known Th1 inhibitors: linomide and pentoxifylline. METHODS: C57BL/6 mice were treated by a single intratracheal instillation of 0.06 mg bleomycin in 0.01 ml saline or saline alone. Treatment groups included: (1) intratracheal bleomycin and daily treatment with linomide or pentoxifylline; (2) intratracheal bleomycin and daily water; (3) intratracheal saline and daily linomide or pentoxifylline; (4) intratracheal saline and daily water. Linomide and pentoxifylline were available per os in the drinking water from 1 day prior to intratracheal instillation. Animals were studied 14 days after intratracheal instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity, fibrosis fraction and alveolar wall area fraction, and by biochemical analysis of lung hydroxyproline content. RESULTS: Linomide or pentoxifylline did not cause any lung injury in saline-treated control mice. Overt signs of lung injury were apparent in bleomycin-treated mice. These changes were not affected by daily treatment with linomide or pentoxifylline, which were given in the highest tolerable dose. CONCLUSION: This study does not support the use of linomide or pentoxifylline to prevent or ameliorate lung fibrosis and may suggest that drug-induced differentiation of T lymphocytes into Th1/th2 subpopulations does not affect the evolution of bleomycin-induced lung injury.

Adjuvants, Immunologic↗

PubMed1998

[Circulating adhesion molecules (cICAM-1, lcVCAM-1) in patients with suspected inflammatory heart muscle disease].

UNLABELLED: Some patients with non-ischemic heart failure show inflammatory changes in the myocardium which are thought to be of causal or pathogenetic relevance for the heart failure. The intercellular adhesion molecule-1 (ICAM-1) and the vascular adhesion molecule-1 (VCAM-1) are membrane proteins with receptor function from the immunoglobulin superfamily which mediate the vascular adhesion and transmigration of leucocytes into the tissue and undergo increased expression in chronic immunological-inflammatory processes. In addition to membrane-bound adhesion molecules, soluble forms can be detected in serum. In the present study we investigated the occurrence and the significance of circulating ICAM-1 and VCAM-1 in 71 patients with non-ischemic heart failure (47 M/24 F, mean age: 55 +/- 11 years). METHODS: Serum concentrations of cICAM-1 and cVCAM-1 were analyzed using ELISA-Kits. The severity of heart failure was assessed in accordance to the NYHA-classification and to hemodynamic parameters (mean pulmonary pressure, left ventricular ejection fraction). Inflammatory heart disease was assessed histologically and immunohistologically (T-lymphocytes > 7.0/mm2, increased expression of the histocompatibility antigens of class I and II) in right ventricular endomyocardial biopsies. 16 healthy, age-matched patients (8 M/8 F, mean age: 55 +/- 6 years, mean ejection fraction 76 +/- 3%) without signs of inflammation in the myocardium (mean T-lymphocytes < 3.5 cells/mm2, low expression of HLA-class I and II) served as controls. RESULTS: The mean serum concentrations of circulating ICAM-1 and VCAM-1 (cICAM-1, cVCAM-1) were higher in patients with non-ischemic heart failure (372 +/- 107 ng/ml and 949 +/- 439 ng/ml) than controls (264 +/- 37 and 710 +/- 164 ng/ml) (p < 0.05). The mean concentrations of both adhesion molecules varied as a function of the mean pulmonary pressure and the left ventricular ejection fracture (for cICAM-1: Pearson's r: 0.24 and -0.33, p < 0.05; for cVCAM-1: Pearson's r: 0.28 and -0.26, p < 0.05). In 38% (n = 16) of patients with elevated concentrations of cICAM-1 (> or = 337 ng/ml) and 41% (n = 7) of those with elevated serum levels of cVCAM-1 (> or = 1038 ng/ml), the myocardial biopsies showed increased lymphocytic infiltration between 7 and 22 T-lymphocytes/mm2 and an enhanced expression of the MHC antigens of class I/II as sign of an activated inflammatory process in the myocardium. All patients with more than 9.3 T-lymphocytes/mm2 in the myocardium (n = 7) had higher serum levels of cICAM-1 (447 +/- 146 ng/ml, p < 0.05 compared to controls) and of cVCAM-1 (1577 +/- 688 ng/ml, p < 0.001). Both adhesion molecules correlated significantly with the mean number of T-lymphocytes in the myocardium (Pearson's r: 0.31-0.37, p < 0.05). SUMMARY AND CONCLUSION: The present study shows that the elevated levels of cICAM-1 and cVCAM-1 are often found in the serum of patients with non-ischemic heart failure. These raised serum levels correlate with inflammatory infiltrates in the myocardial tissue and with the clinical and hemodynamic signs of heart failure, thus, confirming a connection between heart failure and inflammatory changes in the myocardium.

Adult↗

PubMed1998

Peribronchial lymphocyte activation in bleomycin-induced lung injury.

The role of lymphocytes in bleomycin (Bleo)-induced lung injury remains obscure. In normal hamsters, peribronchial lymphatic tissue (PBLT) has been found to contain a large population of T lymphocytes responsive to interleukin 2 (IL-2) but not to IL-4. Lung injury induced by a single intratracheal instillation of Bleo in hamsters has been ameliorated by cyclosporin A (CyA). In the present study, using this model, PBLT-derived lymphocyte function was explored for 28 days after Bleo instillation. Increase in PBLT lymphocytes occurred at five time points investigated, reaching highest values on day +7 (p < 0.0025). Cell proliferation in response to concanavalin A was enhanced, while IL-2 +/- the mitogen had no effect. In contrast to its inactivity in the normal hamster, in the Bleo-injured animal IL-4 alone induced T cell proliferation (p = 0.0077) on day +7. CyA therapy initially suppressed and delayed recovery of the number of lymphocytes and their activation. The results of this study suggest the existence of a vulnerable period in Bleo-induced lung injury and indicate that lymphocytes participate in the pathogenesis of the insult to the tissue. The unresponsiveness to IL-2 and the emergence of cellular response to IL-4 indicate immune deviation in PBLT-derived T cells.

Animals↗

PubMed1998

Use of fiberoptic bronchoscopy in bone marrow transplant recipients.

Bone marrow transplantation (BMT) has become the therapy of choice for a number of malignant and nonmalignant hematologic and nonhematologic disorders. A frequent complication after BMT is pulmonary disease which is associated with a high mortality rate. We examined the results of 79 bronchoscopies performed between May 1991 and May 1995 in 62 patients for the evaluation of pulmonary complications after BMT. In all cases bronchoalveolar lavage (BAL) was performed, in 10% transbronchial biopsy (TBB) was also carried out and in 13% bronchoscopy was followed by open lung biopsy. Positive results were found in 67% of bronchoscopies. Fungal infection (Candida and Aspergillus species) was the most common finding (18%), bacterial infection was found in 13%, mixed (fungal and bacterial) infection in 6%, cytomegalovirus in 11% and Pneumocystis carinii pneumonia in 4%. Diffuse alveolar hemorrhage was detected in 11% of cases. Idiopathic pneumonia syndrome (IPS) was diagnosed by TBB in 3% of procedures. We conclude that BAL is a safe and accurate procedure for the evaluation of pulmonary complications after BMT. TBB should be considered in the absence of thrombocytopenia for the diagnosis of IPS. If bronchoscopy findings are negative, open lung biopsy should be considered.

Adolescent↗

PubMed1997

Colchicine does not ameliorate bleomycin-induced pulmonary injury in hamsters.

We have evaluated the effect of colchicine, a potential antifibrotic drug, on bleomycin-induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a single intratracheal (IT) instillation of bleomycin (bleo). Four groups of male Syrian hamsters each received one of four treatments: (1) IT bleo and twice daily intraperitoneal (IP) injections of colchicine (col) starting one day before IT instillation of bleo (bleo-col); (2) IT bleo and IP injections of saline (bleo-sal); (3) IT saline and IP colchicine (sal-col); and (4) IT saline and IP saline (sal-sal). Animals were sacrificed 28 days after IT treatment. Lung injury was evaluated histologically, biochemically and by analysis of bronchoalveolar lavage (BAL) fluid. Treatment of hamsters with colchicine did not ameliorate the bleo-induced lung injury, as determined by a semiquantitative morphological index that assesses the severity and extent of the lung injury on a scale of 0-3. Lung hydroxyproline measurements and BAL fluid cell count were also similar in bleo-col compared to bleo-sal hamsters. Colchicine did not prevent the bleo-induced restriction expressed by volume displacement. These results indicate that colchicine does not ameliorate the bleo-induced lung inflammation and fibrosis and call for further controlled investigations to justify the use of this drug in pulmonary disorders.

Animals↗

PubMed1997

Bleomycin-induced lung injury is enhanced by interferon-alpha.

We have evaluated the effect of intraperitoneal (I.P.) injection of human recombinant interferon-2alpha (IFN-alpha) on Bleomycin-induced pulmonary injury in hamsters. Pulmonary injury was induced by a single intratracheal (I.T.) instillation of Bleomycin (Bleo). Six groups of male Syrian hamsters were treated as follows: 1) I.T. Bleo and daily I.P. injections of low-dose interferon-alpha (2 x 10(4) U), 2) I.T. Bleo and daily I.P. injections of high-dose interferon-alpha (10(5) U), 3) I.T. Bleo and I.P. injections of saline, 4) I.T. saline and I.P. low-dose IFN-alpha, 5) I.T. saline and I.P. high-dose IFN-alpha, 6) I.T. saline and I.P. saline. Animals were sacrificed 28 days after I.T. treatment. Lung injury was evaluated histologically and biochemically. Treatment of hamsters with low-dose but not high-dose IFN-alpha significantly augmented the Bleo-induced lung injury, as determined by a semiquantitative morphological index. Lung hydroxyproline measurements were highest in Bleo-low-dose-IFN-alpha followed by Bleo-high-dose-IFN-alpha and Bleo-Sal as compared to Sal-Sal and Sal-IFN-alpha controls. These results suggest that IFN-alpha augments Bleo-induced lung injury but that this effect is complex and does not follow a simple-dose-response pattern.

Animals↗

PubMed1997

Differential diagnosis of pleural effusion by lactate dehydrogenase isoenzyme analysis.

STUDY OBJECTIVE: To determine the diagnostic value of pleural fluid lactate dehydrogenase (LDH) isoenzyme analysis in the differential diagnosis of pleural fluid. PATIENTS AND METHODS: Eighty-seven consecutive patients with pleural effusion caused by congestive heart failure (33), infection (33), and malignancy (21) comprised a derivation set of patients. Pleural fluid LDH activity and isoenzyme pattern were established in all patients and analyzed by the classification and regression trees (CART) method. An additional group of 20 consecutive patients comprised a validation set that was used for cross-validation of CART-derived decision tree. RESULTS: A decision tree, with a positive predictive value of 83%, was constructed and validated by data from a validation set of patients. CONCLUSIONS: Pleural fluid LDH isoenzyme pattern may be helpful for the differential diagnosis of the most common causes of pleural effusions: congestive heart failure, infections, and malignancy.

Algorithms↗