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PubMed2003

[Levels and distribution of 15 rare earth elements in tumor and normal lung tissue from the patients with lung cancer].

Ten tumor tissue and normal tissue around tumors were collected from the patients with lung cancer. After digested by mixed acids(HNO3:HClO4 = 10:1), 15 rare-earth elements (REEs) in the tissue were measured directly by ELAN 5000 ICP-MS. Tissue levels and distribution of 15 REEs were analyzed and compared with those in healthy human lung tissue measured in the same condition. Re (rhenium) was used as an internal standard element to compensate for matrit inhibition and sensitivity drift. Recoveries of standard addition for REEs was 92.9%-111.3% and the precision was 0.96%-3.07%. Results showed that levels of 15 REEs in normal tissues around the tumor was as 2.07-2.51 times high as those in the tumor tissue, while the REE distribution curves of them was similar. There were positive abnormalities of Ce and negative abnormalities of Eu in REE curves of both tissue after chondrite-normalized. Compared REE level and distribution pattern in normal tissue with those in tumor tissue from patients with lung cancer, it was found that contents of light REE in lung tissue of health human were much higher while the contents of media and heavy REE were much lower. LREE/HREE in the tumor tissue and normal tissue with lung cancer and health human lung tissue were 12.99, 13.72 and 44.11 respectively. This study suggested that there might be light REEs accumulation in human lung tissue compared with REE distribution in the air particulates and soil. Light REEs accumulation in the lung of healthy people was more obviously than that in patients with lung cancer.

Adult↗
PubMed2004

[Developmental mechanism of the "lung ball"--with reference to the pathological findings of the lung in two resected cases].

The lung ball is a special type of pulmonary aspergillosis (PA) occurring often after chemotherapy for leukemia. Histologically the ball, with air crescent sign on roentgenogram, is compatible with necrotizing lung tissue admixed with Aspergilli. The lung ball differs entirely from the common "fungus ball" in its quality, though they are similar in roentgenological appearances. The present two cases were leukemia which showed pulmonary findings in their therapeutic course, resulting in lung resection. In both cases the lung ball was confirmed histopathologically. Immunostaining of the lung tissue for neutrophil elastase showed elastase in various sites in the bronchial wall, pulmonary blood vessels (artery, vein) and cavitary wall. In our previous studies, much importance was attached to the disturbance of the pulmonary circulation caused by fibrin deposition as a factor in the developmental course of the fungus ball type aspergillosis (semi-invasive type). The circulatory disturbance of the lung was recognized also in the present cases. This two-way destruction of the pulmonary tissue, resulting from both neutrophil elastase activities and pulmonary circulatory disturbances, were regarded as the most important factor for the development of the lung ball. There are few studies on aspergillar lung ball with regard to the above respects.

Aged↗
PubMed1992

Platelet activating factor antagonist enhances lung preservation in a canine model of single lung allotransplantation.

Optimal techniques for lung preservation are yet to be defined. Platelet activating factor is a phospholipid released by a variety of cells and produces pulmonary abnormalities similar to posttransplantation pulmonary dysfunction. We investigated the strength of the effect of the platelet activating factor antagonist BN 52021 as compared with that of deferoxamine, an iron chelator previously shown to improve lung preservation. Differential lung function and pulmonary hemodynamics were used to assess preservation after a 6-hour period of cold ischemic storage in a modified canine model of left lung allotransplantation. Thirty size- and weight-matched mongrel male dogs were used for 15 transplant procedures randomized to one of three preservation techniques. The University of Wisconsin solution was used as the basic flush solution for all experimental animals. BN 52021 was added to the flush solution in one group (10 mg/kg, n = 5) and deferoxime in another group (10 mg/kg, n = 5). No additives were used for the control animals (n = 5). BN 52021 and deferoxime were administered to respective donor animals 30 minutes before organ harvesting (10 mg/kg) and to recipient animals 30 minutes before reperfusion (10 mg/kg). The pulmonary artery flush solution was administered (40 ml/kg) over 4 minutes. Recipient animals received double-lumen endotracheal tubes and were monitored with balloon-tipped, flow-directed catheters in both pulmonary arteries and dual-angle ultrasonic flow probes around each pulmonary artery. Solid-state high-fidelity micromanometers were used to measure pressures in the pulmonary artery, the left atrium, and the left ventricle. Systemic arterial, right and left pulmonary venous, and mixed venous blood samples were analyzed at 1, 2, 4, and 6 hours after transplantation. Pulmonary venous oxygen tension of the transplanted lung for the control group was 202 +/- 81 mm Hg versus 282 +/- 53 mm Hg for the BN 52021 group 6 hours after transplantation (p less than 0.05). Pulmonary vascular resistance of the transplanted lung for the control group was 319 +/- 54 dynes.sec.cm-5 versus 149 +/- 71 dynes.sec.cm-5 for the BN 52021 group (p less than 0.05). Proton magnetic resonance spectroscopy was performed on segments of upper and lower lobes of the native and transplanted lung from recipient animals to determine total lung water content. The BN 52021 group had a total lung water content of 57.3% as compared with 51.9% for the deferoxime group (p = not significant) and 88.6% for the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed1992

Successful twenty-four-hour lung preservation with donor core cooling and leukocyte depletion in an orthotopic double lung transplantation model.

Donor core cooling with cardiopulmonary bypass is a valid method of clinical lung preservation. However, organ ischemia with this method is still limited to short-term intervals. Since circulating leukocytes participate in postischemic injury through the release of oxygen-derived free radicals, we examined whether leukocyte depletion by mechanical filtration could extend ischemic tolerance of the lung during preservation and subsequent double lung transplantation. Bovine donor lungs were preserved by donor core cooling (10 degrees to 15 degrees C) with cardiopulmonary bypass. Donor lungs were removed, stored in 4 degrees C donor blood for 24 hours, and transplanted. Graft function was studied for 6 hours after transplantation. Group 1 animals (n = 6) underwent standard cardiopulmonary bypass with whole blood for donor and recipient procedures. In group 2 (n = 6), leukocyte filters were incorporated into the cardiopulmonary bypass circuit in both donor and recipient operations. In group 2 recipient animals leukocyte counts decreased to 3% of mean baseline values and remained low during the experiment. Postischemic lung function (assessed by systemic arterial oxygenation, pulmonary artery pressure, pulmonary vascular resistance, airway pressure, lung water content, and end-point histologic characteristics) was significantly better preserved in the animals with leukocyte depletion. Leukocyte depletion by mechanical filtration in both donor and recipient improves the ischemic tolerance of the lung beyond that provided by donor core cooling alone, resulting in excellent lung function after 24 hours of ischemia.

Animals↗
PubMed1992

A new technique for double lung transplantation. "Bilateral single lung" transplantation.

Two techniques are currently practiced to achieve bilateral lung transplantation for the treatment of patients with end-stage pulmonary disease associated with infection: heart-lung transplantation, which is illogical, and double lung transplantation by the Toronto technique, which is difficult and entails tracheal complications. After our short experience with single lung transplantation without any bronchial problems, we have performed three double lung transplantations by a new technique, "bilateral single lung" transplantation. After a sternal bithoracotomy, first one lung was transplanted and then the other, without cardiopulmonary bypass. This bilateral single lung transplantation provides all the advantages of single lung transplantation and is particularly recommended for use in patients with severe pleural adhesions.

Adult↗
PubMed1996

Actuarial survival of heart-lung and bilateral sequential lung transplant recipients with obliterative bronchiolitis.

BACKGROUND: Obliterative bronchiolitis is a progressive form of obstructive airway disease that threatens long-term survival in lung transplant recipients. Its incidence and the long-term survival of lung transplant recipients with obliterative bronchiolitis are unknown. METHODS: The results of 89 heart-lung and 13 bilateral sequential lung transplant survivors beyond 90 days of their operation were analyzed. The date of diagnosis for obliterative bronchiolitis was established histologically (presence of submucosal fibrosis) or physiologically by a persistent reduction in the forced vital capacity to less than 0.7 for greater than 6 weeks. There were 43 patients without obliterative bronchiolitis and 59 patients with obliterative bronchiolitis. RESULTS: No differences were found in the mean age and gender ratios between the two groups. The actuarial 1-, 5-, and 10-year percentage freedom from obliterative bronchiolitis was 72 +/- 4.6, 30 +/- 5.6, and 15 +/- 7.4, respectively, with a median onset of 689 days (range 55 to 3404 days). About half the patients with biopsy-proven obliterative bronchiolitis had a fall in their forced expiratory flow at 50% of forced vital capacity/forced vital capacity nearly 4 months before fulfilling the forced expiratory volume in 1 second criteria established by the Working Group on chronic lung dysfunction. The actuarial 1-, 5-, and 10-year percentage survival of obliterative bronchiolitis negative patients was 90 +/- 4.5, 74 +/- 8.4, and 66 +/- 10.6, respectively, versus 90 +/- 3.9, 49 +/- 6.9, and 27 +/- 10.0, respectively, for obliterative bronchiolitis positive patients (p = 0.38). The actuarial 1-, 3-, 5-, 8-, and 10-year percentage survival of lung transplant recipients after the diagnosis of obliterative bronchiolitis was 74 +/- 5.8, 50 +/- 7.5, 43 +/- 7.8, 23 +/- 8.7, and 11 +/- 9.1, respectively, with a median survival of 1084 days (range 0 to 3442 days). CONCLUSIONS: The forced expiratory flow at 50% of forced vital capacity/forced vital capacity is a more sensitive indicator for the early detection of obliterative bronchiolitis than the forced expiratory volume in 1 second after heart-lung or bilateral sequential lung transplantation. The obliterative bronchiolitis negative group survival tends to be better than the obliterative bronchiolitis positive group. The obliterative bronchiolitis positive lung transplant recipients have reasonable outcomes with a median survival time of nearly 3 years after the diagnosis of obliterative bronchiolitis. Earlier detection of obliterative bronchiolitis and refinements in management may further improve these results.

Actuarial Analysis↗
PubMedDate not supplied

Expression of lung-resistance protein gene is not associated with platinum drug exposure in lung cancer.

BACKGROUND: Platinum drug resistance is an important problem in lung cancer chemotherapy. In this study, we examined lung-resistance protein (LRP) gene expression in vivo and in vitro in relation to platinum drug exposure. MATERIALS AND METHODS: The expression levels of the LRP gene were assessed by the reverse transcription polymerase chain reaction, in 80 autopsy samples (40 lung tumors and 40 corresponding normal lung tissues), two lung cancer cell lines and in peripheral mononuclear cells collected from 8 lung cancer patients before and after platinum drug administration. RESULTS: The LRP gene expression levels of autopsy specimens exposed antemortem to platinum drugs were not significantly different to those of specimens without platinum drug exposure, for both lung tumors and normal lung tissues. Our results also demonstrate that LRP gene expression was not induced by platinum drugs either in vitro or in vivo. CONCLUSIONS: The present results indicate that LRP gene expression is not associated with platinum drug exposure in lung cancer.

Adenocarcinoma↗
PubMed2000

Effect of preoperative hyperinflation on static lung volumes after lung transplantation.

It is still not known whether persistent increases in functional residual capacity (FRC) and residual volume (RV) after lung transplantation are due to preexisting hyperinflation. Therefore, the aim of this study was to determine the effects of chronic lung hyperinflation on static lung volumes after heart/lung (HLT) and bilateral lung transplantation (BLT). Static lung volumes were measured in 33 patients before and at 6 month intervals for up to 3 yrs after HLT (n=25) or BLT (n=8). The preoperative diagnosis was cystic fibrosis in 25 patients and other chronic hyperinflated lung diseases in eight patients. After surgery, total lung capacity returned to predicted normal values but FRC and RV remained greater than expected for either the recipient or the donor. At 1 yr after surgery, mean+/-SD FRC and RV were 130+/-18% and 151+/-34% of the predicted values for the recipient (p<0.001), and these figures did not change significantly over time. Similar abnormalities were found in patients with and without cystic fibrosis. After transplantation for lung diseases producing chronic hyperinflation, there is a persistent increase in functional residual capacity and residual volume. This alteration is present in patients operated on for diseases developed in both childhood and adulthood and is not recovered over time. It may be due to irreversible changes in the structure of the ribcage.

Adult↗
PubMed2002

Myeloperoxidase (MPO) genotype and lung cancer histologic types: the MPO -463 A allele is associated with reduced risk for small cell lung cancer in smokers.

MPO participates in the metabolic activation of tobacco carcinogens such as PAHs. A frequent MPO -463 G-->A polymorphism in the promoter region reduces MPO transcription and has been correlated with >4-fold lower benzo[a]pyrene-DNA adduct levels in the skin of coal tar-treated patients. Four of 7 case-control studies found significantly reduced lung cancer risk associated with the A allele. Due to their different etiologies, we examined whether the MPO genotype affects histologic lung cancer types differentially. A case-control study was conducted in 625 ever-smoking lung cancer patients, including 228 adenocarcinomas, 224 SCCs, 135 SCLCs and 340 ever-smoking hospital controls. MPO genotyping was performed by capillary PCR followed by fluorescence-based melting curve analysis. Combining the MPO -463 (G/A+A/A) genotypes, a protective effect approaching significance (OR = 0.75, 95% CI 0.55-1.01) was observed when comparing all lung cancer cases to controls. Among histologic types of lung cancer, a weak protective effect was found for both adenocarcinoma (OR = 0.81, CI 0.55-1.19) and SCC (OR = 0.82, CI 0.56-1.21); a stronger and significant effect was found for SCLC (OR = 0.58, CI 0.36-0.95; p = 0.029). Our results also suggest that the MPO genotype varies among inflammatory nonmalignant lung diseases. In conclusion, our results emphasize the need for a separate analysis of lung cancer histologic types and an adjustment for inflammatory nonmalignant lung diseases in future MPO-related studies. We confirm that the MPO -463 A variant affords a protective effect against lung cancer risk in smokers, which was strongest for SCLC patients.

Adenocarcinoma↗
PubMed1990

Purification and characterization of a Mr approximately 66,000 lung-derived (paracrine) growth factor that preferentially stimulates the in vitro proliferation of lung-metastasizing tumor cells.

In medium containing low concentrations of serum, rat 13762NF mammary adenocarcinoma cell lines and clones (MTPa and MTC; isolated from the locally growing tumor) of low metastatic potential to lung did not exhibit a growth response to lung-conditioned medium, whereas a highly metastatic cell clone isolated from a spontaneous lung metastasis (MTLn3) did. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was isolated by using a five-step procedure (anion exchange chromatography, Affi-gel blue affinity chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis). The lung-derived factor that stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of Mr approximately 66,000 (non-reduced) or Mr approximately 72,000 (reduced) and possessed a pI of 6.9-7.0. It preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in three tumor systems: rat 13762NF mammary adenocarcinoma, murine B16 melanoma, and murine RAW117 large-cell lymphoma. The factor's growth-stimulatory affect was inactivated by reduction or exposure to high temperature (95 degrees C). Although the growth factor appears to be glycosylated, its molecular weight was not altered by treatment with the protein-deglycosylating agent, trifluoromethane sulfonic acid. Cleavage of the protein by cyanogen bromide resulted in the formation of five fragments. Malignant cell response to this lung-derived paracrine growth factor may be important in the successful formation of lung metastases.

Adenocarcinoma↗
PubMed2003

What is the role of tests of lung function in the management of infants with lung disease?

This review considers whether there is a role for lung function tests in the clinical management of infants with lung disease. The purpose of testing lung function in older subjects, the tests available for infants, and the practical problems of testing lung function in infants are considered. After reviewing all the facts, we suggest that there are four situations in which lung function testing should be recommended for infants, as follows: (1) the infant who presents with unexplained tachypnea, hypoxia, cough, or respiratory distress in whom a definitive diagnosis is not apparent from physical examination and other, less difficult investigations; (2) the infant with severe, continuous, chronic obstructive lung disease who does not respond to an adequate clinical trial of combined corticosteroid and bronchodilator therapy; (3) the infant with known respiratory disease of uncertain severity in whom there is need to justify management decisions; and (4) research and development. A review of 62 recent publications to determine how lung function tests are being used at the present time showed that they are being used overwhelmingly for research. The role of lung function testing in the clinical management of infants has not been established, and research is needed to clarify this situation. We suggest that such studies should explore the role of lung function tests in infants with specific symptoms, signs, or diagnoses, taking into account information from other types of investigation and the cost/benefit/risk ratios.

Child, Preschool↗
PubMed2000

Lipopolysaccharide-induced lung injury in mice. I. Concomitant evaluation of inflammatory cells and haemorrhagic lung damage.

Intratracheal instillation of lipopolysaccharide (LPS) induces an inflammatory response characterized by infiltration of polymorphonuclear neutrophils (PMNs) into the extracellular matrix and by the release of mediators that play a fundamental role in lung damage. In the present study, we developed a mouse model which allows correlation of the inflammatory response and haemorrhagic tissue injury in the same animal. In particular, the different steps of the inflammatory response and tissue damage were evaluated by the analysis of three parameters: myeloperoxidase (MPO) activity in the parenchyma, reflecting PMNs accumulation into the lung, inflammatory cells count in the bronchoalveolar lavage fluid (BALF), reflecting their extravasation, and total haemoglobin estimation in BALF, a marker of haemorrhagic tissue damage consequent to PMNs degranulation. In our experimental conditions, intra-tracheal administration of 10 microg/mouse of LPS evoked an increase of MPO activity in the lung at 4 h (131%) and 6 h (147%) from endotoxin challenge. A significant increase of PMNs in the BALF was noticed at these times with a plateau between the 12nd and 24th h. PMN accumulation produced a time-dependent haemorrhagic lung damage until 24 h after LPS injection (4 h: +38%; 6 h: +23%; 12 h: +44%; 24 h: +129% increase of haemoglobin concentration in the BALF vs. control). Lung injury was also assessed histopathologically. Twenty-four hours after the challenge, diffuse alveolar haemorrhage, as well as PMN recruitment in the interstitium and alveolus were observed in the LPS group. This model was pharmacologically characterized by pretreatment of LPS-treated mice with antiinflammatory drugs acting on different steps of the < >. We demonstrated that: a) betamethasone (1, 3, 10, 30 mg/kg p.o.) reduced in a dose-dependent manner the MPO activity, the number of inflammatory cells and, at the same time, lung injury; b) pentoxifylline, a TNFalpha production inhibitor (200 mg/kg i.p.), inhibited PMN extravasation and lung haemorrhage but it was not able to reduce MPO activity in the lung; c) L-680,833, an anti-elastase compound (30 mg/kg po), decreased significantly only the haemorrhagic lung damage; d) indomethacin, a non steroidal antiinflammatory drug (5 mg/kg p.o.), did not show any effect on any of the parameters considered. In conclusion, our in vivo mouse model is a practical alternative to animal models of ARDS (Adult Respiratory Distress Syndrome) recently described and it permits to dissect and to characterize the different steps of PMNs infiltration and, at the same time, the damage caused by their activation.

Animals↗
PubMed1983

Role of radio-aerosol and perfusion lung imaging in early detection of chronic obstructive lung disease.

The efficacy of radio-aerosol and perfusion lung imaging in the early detection of chronic obstructive lung disease was evaluated in 38 subjects. The subjects included 5 non-smokers, 21 smokers with minimal or no respiratory symptoms and 12 patients with chronic obstructive lung disease. Each subject consented to a respiratory questionnaire, detailed physical examination, chest X-ray examinations, detailed pulmonary function tests and 99mTc-radio aerosol-inhalation lung imaging. Perfusion lung imaging with 99mTc-labelled macroaggregated albumin was performed in 22 subjects. A significant correlation (P less than 0.001) was observed between the degree of abnormalities on radio-aerosol imaging and pulmonary function tests (PFTs) including forced expiratory volume in 1 s, maximum mid-expiratory flow rate and mean transit time analysis. Abnormal radio-aerosol patterns and deranged PFTs were observed in 21 subjects each. Of 21 subjects with abnormal radioaerosol pattern 8 had normal PFTs. Of 21 subjects with abnormal PFTs 8 had normal aerosol images. Aerosol lung images and PFTs were abnormal more frequently than perfusion lung images. The results suggest that radio-aerosol lung imaging is as sensitive an indicator as PFTs for early detection of chronic obstructive lung disease and can be usefully combined with PFTs for early detection of alteration in pulmonary physiology in smokers.

Adolescent↗
PubMed1999

Surgical treatment for metastatic lung tumors with incidentally coexisting lung cancer.

We report four surgically resected cases of a metastatic lung tumors with incidentally coexisting lung cancer. Two patients (Cases 1 and 2) were admitted for surgical treatment for pulmonary metastases from colon cancer, and the other two (Cases 3 and 4) were for pulmonary metastases from renal cell carcinoma. In only one patient (Case 3), one lesion among the multiple shadows on the preoperative computed tomography examination was rather strongly suspected to be primary lung cancer. In three patients (Cases 1, 2 and 3), one of the resected lesions in each individual case was diagnosed as lung adenocarcinoma by an intraoperative examination using frozen sections, and was later histologically confirmed. In Case 4, one of the resected lesions was postoperatively determined to be lung adenocarcinoma. All coexisting lung cancers, treated with partial resection of the lung, were well-differentiated small-sized adenocarcinoma (T1N0), while the other lesions resected in each case were metastases from the individual cancer. Problems in preoperative diagnosis and surgical treatment for metastatic lung tumors with incidentally coexisting lung cancer are discussed.

Adenocarcinoma↗
PubMed2006

Central hemodynamics during lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia. A study by echocardiography and continuous pulmonary artery flow measurements in lung-injured pigs.

OBJECTIVE: The impact of lung-recruitment maneuvers on heart function at different volemic levels has not been studied in detail. We therefore investigated the effect on central hemodynamics of lung recruitment maneuvers at hypovolemia, normovolemia and hypervolemia in experimental lung injury. DESIGN: Randomized, controlled, cross-over experimental study. SETTING: Animal laboratory at a university hospital. PARTICIPANTS: Eleven anesthetized and lung-lavaged pigs. INTERVENTION: The animals were randomized to 10-s lung recruitment maneuvers followed by 30-s maneuvers (40 cm H(2)O airway pressure) or vice versa, performed under hypovolemia, normovolemia and hypervolemia. MEASUREMENTS AND MAIN RESULTS: Left-ventricular end-diastolic diameter and cardiac output were measured before, during, and 1 min and 5 min after the lung recruitment maneuver and left-ventricular eccentricity index was calculated for before and during the maneuver. Cardiac output and left-ventricular end-diastolic diameter (within parentheses) decreased significantly during both the 10-s and 30-s lung recruitment maneuvers at hypovolemia, by a mean of 89% (35) and 92% (33), at normovolemia by 75% (33) and 86% (32), and at hypervolemia by 56% (32) and 64% (43), respectively. At hypovolemia, cardiac output was increased above baseline 1-5 min following the 30-s maneuver. Left-ventricular eccentricity index increased significantly during the maneuver, indicating right ventricular dysfunction. CONCLUSIONS: In this animal lung injury model, lung recruitment maneuvers significantly decreased left-ventricular end-diastolic volume and cardiac output at hypovolemia. Hypervolemia did partly counteract this compromise. In addition, a marked right-ventricular dysfunction during the maneuver was found.

Animals↗
PubMed2005

Lung transplantation for emphysema. Lung hyperinflation: incidence and outcome.

Lung transplantation, single or bilateral sequential, is the final option for patients with emphysema. This study analyzed the outcome of lung transplants for emphysema (single or double), and evaluates the incidence, predictive factors and prognosis of lung hyperinflation (LHI) in unilateral transplants. We prospectively studied patients undergoing lung transplantation for emphysema. On admission to the Intensive Care Unit (ICU) and at 12, 24, 48 and 72 h we tested the patients' respiratory function, oxygen arterial pressure (PaO2) and mean pulmonary arterial pressure (MPAP) before transplantation. LHI incidence, duration of mechanical ventilation and hypoxemia, ICU stay and mortality was also analyzed. We studied 34 consecutive patients undergoing lung transplantation for emphysema, 14 single and 20 bilateral. Single-lung transplantation had a higher mortality (50%) than double-lung transplantation (11%), with an odds ratio of 9.0 (1.3-48.7). Of the 14 patients who received a single graft, 9 patients (64%) developed LHI. No predictive factors for LHI could be established. Duration of mechanical ventilation (22 vs 3 days) and ICU stay (36 vs 6 days) was much longer in patients with LHI; however, only ICU stay reached statistical significance (P = 0.011). Mortality in patients with LHI was higher, 67% vs 20% (NS). We conclude that single-lung transplant in emphysema patients has a worse prognosis than bilateral transplant, with a 9-fold higher mortality rate. LHI is a common event in single-lung transplant for emphysema and is associated in our patients with a longer stay at the ICU.

APACHE↗
PubMed2006

Polycyclic aromatic hydrocarbon (PAH) metabolizing enzyme activities in human lung, and their inducibility by exposure to naphthalene, phenanthrene, pyrene, chrysene, and benzo(a)pyrene as shown in the rat lung and liver.

In order to survey changes and activities in the polycyclic aromatic hydrocarbon (PAH)-metabolizing enzymes implicated in lung cancer susceptibility studies, we investigated enzyme induction by 2-5-ring-sized 'biomarker' PAHs in rat liver and lung, and the activities in five human lung specimens. Naphthalene, phenanthrene, pyrene, chrysene, and benzo[a]pyrene (BaP) were administered to rats for 3 days (25-128 mg/kg/day) and the responses compared with those of model inducers. PAH treatment increased the CYP1A-catalyzed activity of pyrene 1-hydroxylation and 7-ethoxyresorufin O-deethylation in rat liver by up to 28- and 279-fold, and in rat lung by up to 22- and 51-fold, respectively. 1-Naphthol (hUGT1A6), 1-hydroxypyrene (hUGT1A6/1A9), and entacapone (hUGT1A9) are markers of PAH-glucuronidating human uridine diphosphate-glucuronosyltransferases (UGT). These activities increased up to 6.4-fold in rat liver and up to 1.9-fold in rat lung. NADPH:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase activities increased up to 5.3- and 1.6-fold (liver), and up to 4.4- and 1.4-fold (lung), respectively. CYP1A showed the best liver-to-lung relationship (R (2 )=( )0.90). The inducing efficiency by PAHs differed extensively: control 60-fold), many times greater than the experimental (inducible/constitutive) variation in the rat. Kinetics of 1-hydroxypyrene glucuronidation showed two low-K (m) forms both in rat and human lung. Since the 2-4-ring PAHs (major constituents) were poor enzyme inducers, it appears that the PAH-metabolizing pathways are mainly induced by BaP-type minor constituents. Gene-environmental interactions which magnify polymorphic variability in pulmonary bioactivation/detoxification capacity probably play a key role in individual susceptibility to (or protection against) chemically induced lung cancer. Hence, human exposure to PAH mixtures with high content of BaP-type hydrocarbons confers a potentially higher health risk than PAH mixtures with low content of procarcinogens.

Animals↗
PubMed2003

Expression of vascular adhesion protein-1 in normal and inflamed mice lungs and normal human lungs.

Recently, vascular adhesion protein-1 (VAP-1) was implicated in adhesion and transmigration of lymphocytes across endothelial cells in liver and other organs. There is very little information on VAP-1 expression in normal and inflamed lungs. Therefore, we conducted a study to localize VAP-1 in normal mice and human lungs and in two distinct murine models of lung inflammation. Normal mice and human lungs revealed VAP-1 expression in the endothelium of large and mid-sized pulmonary vessels but not in alveolar septae, airway epithelium or blood cells. Mice that lack the lpr(-/-) gene and develop extensive lymphocytic infiltration in their lungs showed VAP-1 expression similar to the normal mice lungs. Mice subjected to cecal ligation and puncture developed acute lung inflammation and showed VAP-1 not only in endothelial cells but also in inflammatory cells in perivascular areas at 72 h after the procedure. We concluded that VAP-1 expression may contribute to the functional heterogeneity of endothelial cells within the lung to create distinct sites for the recruitment of inflammatory cells. Furthermore, since VAP-1 is expressed over a longer period of time in inflamed lungs, it may even be a suitable target for drug delivery and therapeutic manipulations.

Aged↗