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At least 829 records · Page 46Linked to original sources
PubMed2000

Bronchial healing, lung parenchymal histology, and blood gases one month after transplantation of lungs topically cooled for 2 hours in the non-heart-beating cadaver.

BACKGROUND: The aim of this study was to investigate, in an experimental survival model, the functional and morphologic results of lung transplantation using lungs from non-heart-beating donors. METHODS: Left lungs, topically cooled to 25 degrees C for 2 hours in situ after 5 minutes of circulatory arrest followed by 26 minutes of unsuccessful cardiopulmonary resuscitation, were transplanted into syngeneic rats. Five weeks after the transplantation, right pneumonectomy was performed and blood gases measured after 60 minutes. In a control group, fresh donor lungs were used for transplantation and comparison was made with the cadaver group and a group of normal rats after right pneumonectomy. Morphologic changes were evaluated by semiquantitative scoring of 13 different parameters to obtain a total histologic index for each rat. RESULTS: Computerized tomography scans of the chest made during the third post-operative week showed normal lung parenchyma in both groups, and at 5 weeks there were no significant differences in blood gases. The bronchial anastomoses showed normal healing in all cases. The histologic changes in the lung parenchyma were generally mild and focal, primarily consisting of interstitial and perivascular mononuclear inflammation, bronchial inflammation and athelectasis. Surprisingly, the transplanted controls demonstrated the most pronounced changes, although only the difference in total histologic index between groups was significant. CONCLUSIONS: Lungs from non-heart-beating donors, topically cooled in the cadaver for two hours after failed resuscitation, showed normal bronchial healing and favorable parenchymal histology compared to transplanted control lungs 5 weeks after transplantation.

Animals↗
PubMed2003

Variability in standard care for cytomegalovirus prevention and detection in pediatric lung transplantation: survey of eight pediatric lung transplant programs.

Cytomegalovirus (CMV) infection after pediatric lung transplantation is a significant risk factor for morbidity and mortality in the first year after transplantation. Multiple strategies have been reported for CMV prevention among adult lung transplant programs. In contrast, little information has been reported regarding protocols for prevention and detection of CMV from pediatric programs. We conducted a survey to better understand the range of practice patterns for CMV prevention and detection at pediatric lung transplant centers. A self-administered questionnaire was distributed to 11 pediatric lung transplant centers identified through the International Pediatric Lung Transplant Collaborative in September 2002. A member of the lung transplant team from each institution was asked to provide the methods of CMV prevention and surveillance. Eight of 11 centers surveyed responded to the questionnaire accounting for 45.6% (26 of 57) and 100% (three of three) of the pediatric lung transplants performed in the US and UK in 2001, respectively. All centers used prophylactic therapy against CMV with either ganciclovir or valganciclovir with duration ranging from 3.5 wk to indefinitely. Most centers (six of eight) prescribed a prophylactic regimen based on donor and recipient CMV serostatus. Half (four of eight) of the centers report using CMV hyperimmune globulin in addition to an antiviral agent. Method for CMV detection varied widely, including use of conventional viral culture (n = 1), antigenemia (n = 7), and polymerase chain reaction (n = 2). A wide range of strategies is used to prevent and detect CMV in pediatric lung transplant recipients with little empiric evidence demonstrating the optimal approach. A retrospective analysis among these centers is being conducted to evaluate the efficacy of these approaches.

Antiviral Agents↗
PubMed2002

Resolution of native lung pneumothorax by insertion of a nitinol stent for bronchostenosis in the transplanted lung.

Following single lung transplantation, the native lung remains a potential source of morbidity from spontaneous pneumothorax, hyperinflation, bacterial and fungal infection and malignancy. The case of a single lung transplant recipient for idiopathic pulmonary fibrosis who developed a recurrent, non-resolving, spontaneous multiloculated pneumothorax in the native lung following thoracoscopic talc pleurodesis is reported. The pneumothorax ultimately resolved following insertion of a nitinol stent for coexisting bronchostenosis in the transplanted lung. In a single lung transplantation recipient in whom a native lung pneumothorax reoccurs or persists despite appropriate initial management, it may be useful to undertake bronchoscopy to exclude the possibility of bronchostenosis in the transplanted lung.

Adult↗
PubMed2002

Computed tomographic image comparison between mediastinal and lung windows provides possible prognostic information in patients with small peripheral lung adenocarcinoma.

OBJECTIVES: The purpose of this study was to determine whether the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor of small peripheral lung adenocarcinoma. METHODS: We studied the computed tomographic images of 143 patients with primary peripheral lung adenocarcinoma of 30 mm or less in maximum diameter. Two groups were categorized according to the tumor's ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image (tumor's area in the mediastinal computed tomographic image/tumor's area in lung computed tomographic image x 100%), both faint density-type (<50%) and solid-type images (>/=50%). Clinical factors and prognoses of the 2 groups were analyzed. RESULTS: There were 58 patients with the solid-type tumor image and 85 patients with the faint density-type tumor image. The number of patients with tumor size of less than 20 mm in the faint density-type tumor group (n = 30) was significantly higher than that in the solid-type tumor group (n = 8, P =.008). The 5-year survival of patients with faint density-type tumors was 74.1%, whereas that in patients with solid-type tumors was 54.2% (P =.013). Furthermore, the survival curve of patients with the solid-type computed tomographic image combined with ground-glass opacity was similar to that of patients with the faint density-type image. Multivariate analysis revealed the prognostic influence of the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image on survival (P =.029, relative risk = 0.48) and showed to be of second highest influence after the N factor. CONCLUSIONS: It is suggested that the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor in patients with small peripheral lung adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Transforming growth factor-beta 1 and its receptors in human lung cancer and mouse lung carcinogenesis.

The transforming growth factor-betas (TGF-beta s) are multifunctional proteins that inhibit the proliferation of many epithelial cells through a set of cell protein receptors that includes the TGF-beta type I (RI) and type II (RII) receptors. Loss of growth inhibition by TGF-beta is thought to contribute to the development of many types of tumors. In the present study, we have examined expression of the proteins and mRNAs for TGF-beta 1, TGF-beta RI, and TGF-beta RII in normal human lung, well-characterized non-small cell lung cancer (NSCLC) cell lines, and primary NSCLC specimens. Immunohistochemical staining for TGF-beta 1, TGF-beta RI, and TGF-beta RII using specific antibodies in normal human lung showed expression of the 3 proteins in the epithelium of bronchi and bronchioles as well as in alveoli. Differential expression of TGF-beta RI and TGF-beta RII proteins was detected in 5 NSCLC cell lines using Western blot analysis, with reduced levels in 3 cell lines. A panel of 45 formalin-fixed and paraffin-embedded NSCLC specimens showed positive immunostaining for TGF-beta 1, TGF-beta RI, and TGF-beta RII, with reduced TGF-beta RII in poorly differentiated adenocarcinomas and squamous cell carcinomas and some moderately differentiated adenocarcinomas. In situ hybridization studies conducted with specific riboprobes for TGF-beta 1, TGF-beta RI, and TGF-beta RII showed corresponding localization of expression of the mRNAs in the specimens that showed positive immunostaining for the proteins. To investigate the roles of TGF-beta 1, TGF-beta RI, and TGF-beta RII in chemically induced mouse lung tumorigenesis, we examined the expression of their proteins and mRNAs in 2 mouse model systems. Whereas expression of the proteins and mRNAs for TGF-beta 1 and TGF-beta RI was comparable in lung adenomas and bronchioles of A/J mice treated with benzo(alpha)pyrene, decreased immunostaining and hybridization for TGF-beta RII protein and mRNA was detected in 50% of lung adenomas in these mice. Interestingly, expression of TGF-beta 1 and the TGF-beta receptor proteins was similar to that of bronchioles in C57B1/6 mice and their littermates heterozygous for deletion of the TGF-beta 1 gene treated with diethylnitrosamine. These data show that reduced levels of expression of TGF-beta RII occur in some, but not all, human and mouse lung tumors. This suggests that different mechanisms of action, some of which may involve the TGF-beta signaling pathway, may contribute to the progression of lung tumorigenesis.

Adenoma↗
PubMedDate not supplied

Estimation of gas and tissue lung volumes by MRI: functional approach of lung imaging.

PURPOSE: The purpose of this work was to assess the accuracy of MRI for the determination of lung gas and tissue volumes. METHOD: Fifteen healthy subjects underwent MRI of the thorax and pulmonary function tests [vital capacity (VC) and total lung capacity (TLC)] in the supine position. MR examinations were performed at inspiration and expiration. Lung volumes were measured by a previously validated technique on phantoms. Both individual and total lung volumes and capacities were calculated. MRI total vital capacity (VC(MRI)) was compared with spirometric vital capacity (VC(SP)). Capacities were correlated to lung volumes. Tissue volume (V(T)) was estimated as the difference between the total lung volume at full inspiration and the TLC. RESULTS: No significant difference was seen between VC(MRI) and VC(SP). Individual capacities were well correlated (r = 0.9) to static volume at full inspiration. The V(T) was estimated to be 836+/-393 ml. CONCLUSION: This preliminary study demonstrates that MRI can accurately estimate lung gas and tissue volumes. The proposed approach appears well suited for functional imaging of the lung.

Adult↗
PubMed2000

Endothelin receptor antagonist SB209670 decreases lung allograft apoptosis and improves lung graft function after prolonged ischemia.

Apoptosis has been postulated as a contributing factor in ischemia-reperfusion graft dysfunction following lung transplantation. The purpose of this study was to determine whether treatment with an endothelin-A/endothelin-B- (ET(A)/ET(B)) receptor antagonist could reduce the level of apoptosis observed in the lung following ischemia-reperfusion injury. Eleven dogs were subjected to left lung allotransplantation. Heart-lung blocks were harvested from donor dogs and preserved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 h. We investigated the level of apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), in the lungs of animals receiving an intravenous infusion of saline (control, n = 5) or the ET receptor antagonist SB209670 (n = 6) (15 microg/kg/min). The infusion began 30 min prior to transplantation and continued for up to 6 h thereafter. The TUNEL staining was significantly higher in the airway epithelium and the parenchyma of the saline (control) group (40.67 +/- 6.16), compared with native right lungs (5.00 +/- 0.56) and the treatment group (14.13 +/- 2.84). We conclude that treatment of lung allografts with the mixed ET(A)/ET(B)-receptor antagonist SB209670 can ameliorate lung injury by reducing the level of apoptosis seen in the allograft following ischemia-reperfusion injury.

Animals↗
PubMed1995

Distinct phenotypes of infiltrating cells during acute and chronic lung rejection in human heart-lung transplants.

To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung rejection, as diagnosed by clinical data and histopathological investigation. TBBs without rejection and normal lung tissue specimens served as controls. Distinct phenotypes of inflammatory cells were found in acute and chronic lung rejection. T cells were present both in acute and in chronic rejection, but did not differentiate between them. In contrast, B cells with antibody deposition were mainly present in chronic rejection and not in acute rejection. Activated macrophages were present only in acute rejection and not in chronic rejection. In nonrejecting lung transplants, perivascular infiltrating cells were virtually absent. In the biopsy specimen, vessels had to be available for analysis, because the cell phenotypes were best recognized in perivascular infiltrates. The analysis of specific phenotypes of inflammatory cells by immunohistochemistry supports the diagnosis of acute and chronic lung rejection, in particular in those cases in which TBB provides limited tissue without airways.

Antibodies, Monoclonal↗
PubMed1997

Analysis of CYP2D6 expression in human lung: implications for the association between CYP2D6 activity and susceptibility to lung cancer.

We have studied whether CYP2D6 is expressed in human lung tissue, using a specific and sensitive reverse transcriptase-polymerase chain reaction method and immunohistochemistry. Seven out of the eight patients were extensive metabolizers as shown by genotyping for the CYP2D6 (debrisoquine-sparteine) polymorphism. To investigate whether expression of CYP2D6 in lung tumours is different from that in normal lung tissue, tumour tissue samples were also obtained from the same eight patients. Correctly spliced CYP2D6 mRNA was detected by RT-PCR analysis in human liver and duodenum but not in any of the lung samples. In accordance with these negative results, immunoreactivity for CYP2D6 protein, using specific monoclonal and polyclonal antibodies, was very low or absent. No specific cell type of lung tissue showed strong immunoreactivity for CYP2D6, although expression of CYP3A could be clearly demonstrated in the same tissue samples. Moreover, a Western blot analysis revealed no signal in lung microsomes from two additional extensive metabolizers. Taken together, these results indicate that expression of CYP2D6 in human lung is absent or very low. These findings thus argue against a significant local metabolic activation of procarcinogenic agents by CYP2D6 in the lung.

Aged↗
PubMed2005

Bilateral lavage with diluted surfactant improves lung function after unilateral lung contusion in pigs.

OBJECTIVE: This study evaluates the effects of bronchoalveolar lavage with diluted surfactant on unilateral lung contusion-induced lung dysfunction. DESIGN: Randomized prospective animal study. SETTING: An animal laboratory. SUBJECTS: Twenty adult pigs, weighing 25-35 kg. INTERVENTIONS: Animals were randomly assigned to controls and surfactant treatment. Bilateral lavage with surfactant treatment began 30 mins after unilateral lung contusion. Then 25 mg/kg of body weight diluted Curosurf (5 mg/mL) was applied in a volume of 5 mL/kg of body weight. Observation time was 8 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: The Pao2/Fio2 ratio fell from 500 to 250 and then recovered gradually in controls and surfactant-treated pigs. After another 4 hrs, the Pao2/Fio2 ratio deteriorated again in controls, but not in surfactant-treated animals. Total compliance fell by 50% after injury but was completely restored by surfactant treatment. Lung contusion increased the median number of neutrophils in bronchoalveolar lavage fluid from 2% to 30% of total cells and peaked >60% at 480 mins in the contused lungs of control pigs. Surfactant-treated pigs had 40% neutrophils at 480 mins without reaching significant difference to controls. The leukocyte neutral proteinase inhibitor increased to 500 ng/mL at 30 mins postinjury in the contused lungs and increased to 2000 ng/mL after surfactant treatment. CONCLUSIONS: Bilateral bronchoalveolar lavage with diluted surfactant can effectively improve lung function after experimental unilateral lung contusion in pigs.

Animals↗
PubMed2005

Lung transplantation and interstitial lung disease.

PURPOSE OF REVIEW: Interstitial lung disease includes a heterogeneous group of disorders that leads to respiratory insufficiency and death in a significant number of patients. Lung transplantation is a therapeutic option in select candidates. RECENT FINDINGS: The indications, transplant procedure options, and outcomes continue to evolve. Various recipient comorbidities influence the choice of procedure in patients with interstitial lung disease. Single lung transplants are used as the procedure of choice and bilateral transplants are reserved for patients with suppurative lung disease and patients with pulmonary hypertension. Issues unique to patients with interstitial lung disease affect the morbidity, mortality and recurrence of the disease. SUMMARY: Lung transplantation is an effective therapy for respiratory failure in interstitial lung disease with survival following transplant being similar to that achieved in transplant recipients with other diseases.

Comorbidity↗
PubMed2006

Normothermic ex vivo lung perfusion of non-heart-beating donor lungs in pigs: from pretransplant function analysis towards a 6-h machine preservation.

Donor shortage urges optimal use of all lungs available. Ex vivo lung perfusion (EVLP) is a method to evaluate lung function before implantation. EVLP was performed in pigs to evaluate lung function, using two different clinical non-heart-beating (NHS) donor protocols: flush perfusion and topical cooling after 1-h warm ischaemia (n = 5 each). Secondly, we investigated whether EVLP can be used for 6 h ex vivo machine preservation (n = 4). In comparison with topical cooling, flush perfusion preserved lung function better during EVLP. During 6 h normothermic EVLP, gas exchange remained stable; however, the pulmonary artery pressure and ventilation pressure showed a significant increase. EVLP is a reliable method for evaluation of lung graft function. Flush perfusion with Perfadex is preferred above topical cooling in NHB lung donation. Six-hour normothermic EVLP is feasible but should be further improved to make ex vivo machine preservation or treatment of lung grafts successful.

Animals↗
PubMed2006

CMV-specific CD8 T-cell dynamics in the blood and the lung allograft reflect viral reactivation following lung transplantation.

Despite the potentially high burden of cytomegalovirus (CMV)-related disease following lung transplantation, the role of the cytotoxic T-lymphocyte (CTL) response to CMV in this patient group is ill-defined. We assessed the CMV-specific T-cell response in the blood and lung allograft of immunosuppressed lung transplant recipients receiving antiviral prophylaxis and following their withdrawal. While the proportion of CMV-specific CTL varied between patients, in the absence of CMV reactivation the level of CMV-specific CD8+ T cells in the blood remained stable over time. In the majority of patients CMV-specific cells could be detected in the lung allograft, often in the absence of viral DNA. Additionally, following primary CMV lung infection, CMV-specific CD8+ T cells were detected no earlier than 100 days post-transplantation but still prior to the detection of viral DNA in the lung allograft. Together these findings suggest that very low levels of CMV replication are sufficient to both prime and recruit CMV-specific CD8+ T cells to the MHC-mismatched lung allograft. The direct detection of CMV-specific T cells with an effector phenotype in the lung allograft suggests a protective antiviral function. This study provides a framework upon which the association between CMV and chronic allograft rejection can be further studied.

Adult↗
PubMed1980

Chromium content of lungs of chromate workers with lung cancer.

The chromium content was measured in the lungs of chromate workers, obtained at necropsy in six patients and at surgery in two. The mean chromium content of peripheral lung tissue was 36.7 micrograms per gm wet weight (range 0.50 to 130.2 micrograms) and that of the large airways was 0.51 micrograms per gm wet weight (range 0.22 to 0.99 micrograms). These means values were high compared with those from control lungs of a non-chromate exposed lung cancer patients--respectively 0.21 micrograms per gm in lung tissue and 0.11 micrograms per gm in the large bronchi. The longer the exposure period, the higher was the chromium content in the lungs. The concentration of chromium in the upper lobes was significantly higher than that in the lower lobes, suggesting regional differences either in clearance from or deposition in the lung. Moreover, it was apparent that the metal remained in the lungs long after exposure to chromate had ceased

Aged↗
PubMed1985

Effect of increases in lung volume on clearance of aerosolized solute from human lungs.

To study the effect of increases in lung volume on solute uptake, we measured clearance of 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosol (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH2O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.

Aerosols↗
PubMed1998

Elevated serum sialyl Lewis X-i antigen levels in non-small cell lung cancer with lung metastasis.

To evaluate the relationship between serum levels of sialyl Lewis X-i antigen and lung metastasis in patients with non-small cell lung cancer (NSCLC), we measured the serum level of the antigen in 299 patients with untreated locally advanced or metastatic NSCLC. Before treatment, serum levels of sialyl Lewis X-i antigen were significantly higher in patients with lung metastasis than in those without lung metastatis (p = 0.0001). Of 201 patients without lung metastasis at the time of primary diagnosis, 121 patients died between July 1987 and December 1995. Serum levels of sialyl Lewis X-i antigen in 21 patients who developed lung metastasis during the period were significantly higher than those in 100 patients who did not develop lung metastasis (p = 0.0171). Our results suggested that sialyl Lewis X-i antigen might be a good indicator for the presence or development of lung metastasis, and it might provide clinical information about the management of patients with NSCLC.

Aged↗
PubMed1997

Computed tomographic measurement of lung density changes in lung water with hemodialysis.

In 10 hemodialysis patients, with an ultrafiltration volume ranging from 1 to 4.5 liters per session, the lung density was measured by computed tomography (CT) and the lung volumes by total body plethysmography. From the CT numbers (difference in X-ray attenuation between lung and water, measured in Hounsfield units, HU), and by using a special computer program, quantitative estimates of the densities of normally inflated (pixels between -1,000 and -500 HU), poorly inflated (pixels between -500 and -100 HU) and noninflated lung tissue (pixels between -100 and +100 HU) were obtained. The sizes of the normally and poorly inflated areas were also measured. The results showed that, after dialysis, the normally inflated area was decreased in density and increased in size, and conversely, the size of the poorly inflated area was diminished but without change in density. This finding implied introduction of more gas into the lung. The above observation was reflected by the results of pulmonary function measurements, in that the total lung capacity and functional residual capacity were significantly increased after dialysis. In conclusion, changes in lung fluid (both intra- and extravascular) with hemodialysis can be measured quantitatively by the changes in lung density as estimated by the CT densitometry technique.

Adult↗
PubMed1987

Ambroxol increases the choline but not fatty acid incorporation into lung phospholipids in experimental lung disorders.

Ambroxol, a drug capable of elevating the phospholipid content in healthy rabbit lungs, was tested on two models of experimental lung injury, lung changes in sepsis induced by a peritonitis and in bromcarbamide intoxication. The phospholipid content of the lungs and the synthesis of the individual phospholipids phosphatidylcholine (PC) and sphingomyeline were measured in vitro by incubation of lung slices with labeled phospholipid precursors. Influenced by the drug, the phospholipid content increases to 132% in the peritonitis experiments and to 111% in the bromcarbamide experiments. The peritonitis experiments show the increase in phospholipid synthesis to result from an enhanced choline incorporation into PC up to 192% and into sphingomyeline up to 630%. The values for the bromcarbamide experiments are 411% for PC and 485% for sphingomyeline, respectively. There was no statistically significant difference in the incorporation of fatty acids in the treated and untreated animals. We conclude that ambroxol possibly stimulates the phospholipid synthesis in injured lungs by stimulating the choline phosphatcytidyltransferase, but not the incorporation of fatty acids into PC in those lungs. These findings may be important to the surfactant system of the lung consisting mainly of PC.

Ambroxol↗