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The prognostic value of perfusion lung scintigraphy in patients who underwent single-lung transplantation for emphysema and pulmonary fibrosis.

UNLABELLED: The objective of this study was to evaluate the role of quantitative perfusion lung scintigraphy (QPLS) in predicting the development of chronic rejection in patients who underwent single-lung transplantation. METHODS: Eighteen patients (15 men, 3 women; age range, 41-60 y; mean age, 54.6+/-6.0 y) who underwent single-lung transplantation for emphysema (n = 14) or pulmonary fibrosis (n = 4) were studied. Patients were evaluated using QPLS and pulmonary function tests before surgery and at 1-3 mo and 1-3 y after transplantation. Relative perfusion of the transplanted lung was calculated from standard perfusion lung scintigrams. Values for forced expiratory volume in the first second (FEV1) were obtained from lung function tests at the same time points. The maximal and minimal relative perfusion and FEV1 values in the early (1-3 mo) and late (1-3 y) follow-up periods were identified for each patient. Receiver operating curve (ROC) analysis was performed on all parameters. RESULTS: In total, 82 lung scans were performed (mean, 4.8+/-1.55 per patient) and 484 FEV1 test determinations were obtained (mean, 30.0+/-15.6 per patient) during a follow-up period ranging from 8 to 84 mo (mean, 39.6+/-19.3 mo). In 7 of the 18 patients, chronic rejection developed, whereas 11 patients had a favorable outcome. No significant difference was found in the number of complications (acute rejection and infection episodes) between patients with a favorable outcome and patients with chronic rejection, up to 1 y after transplantation. At 1-3 mo, minimal relative perfusion values were 67.1%+/-12.2% in the favorable outcome group and 50.8%+/-9.6% in the chronic rejection group (P = 0.02). Before surgery and at 1-3 y, minimal relative perfusion was not significantly different between the 2 groups. The difference in maximal relative perfusion at 1-3 y was marginally significant, with 76.5%+/-8.9% in the favorable group and 64.3%+/-15.0% in the chronic rejection group (P = 0.051). FEV1 values were not significantly different preoperatively and 1-3 mo after surgery between the chronic rejection and the favorable outcome groups. Late in the follow-up period (1-3 y), FEV1 values in the chronic rejection and favorable outcome groups were 35.6%+/-7.9% and 56.9%+/-13.6%, respectively (P = 0.002). ROC analysis of minimal relative perfusion at 1-3 mo identified a threshold of 57% under which the sensitivity and specificity for chronic rejection were 83% and 88%, respectively. Minimal FEV1 for the same period identified a threshold of 48% under which the sensitivity and the specificity were 80% and 67%, respectively. CONCLUSION: QPLS early after transplantation in our patients predicted the development of chronic rejection in patients with single-lung transplantation for emphysema and pulmonary fibrosis, whereas surgical complications, acute rejection, infection episodes, and lung function tests did not predict the outcome. This early prediction could not be obtained from lung function tests performed at the same time.

Adult↗

The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium.

We used overlapping and nested homozygous deletions, contig building, genomic sequencing, and physical and transcript mapping to further define a approximately 630-kb lung cancer homozygous deletion region harboring one or more tumor suppressor genes (TSGs) on chromosome 3p21.3. This location was identified through somatic genetic mapping in tumors, cancer cell lines, and premalignant lesions of the lung and breast, including the discovery of several homozygous deletions. The combination of molecular manual methods and computational predictions permitted us to detect, isolate, characterize, and annotate a set of 25 genes that likely constitute the complete set of protein-coding genes residing in this approximately 630-kb sequence. A subset of 19 of these genes was found within the deleted overlap region of approximately 370-kb. This region was further subdivided by a nesting 200-kb breast cancer homozygous deletion into two gene sets: 8 genes lying in the proximal approximately 120-kb segment and 11 genes lying in the distal approximately 250-kb segment. These 19 genes were analyzed extensively by computational methods and were tested by manual methods for loss of expression and mutations in lung cancers to identify candidate TSGs from within this group. Four genes showed loss-of-expression or reduced mRNA levels in non-small cell lung cancer (CACNA2D2/alpha2delta-2, SEMA3B [formerly SEMA(V), BLU, and HYAL1] or small cell lung cancer (SEMA3B, BLU, and HYAL1) cell lines. We found six of the genes to have two or more amino acid sequence-altering mutations including BLU, NPRL2/Gene21, FUS1, HYAL1, FUS2, and SEMA3B. However, none of the 19 genes tested for mutation showed a frequent (>10%) mutation rate in lung cancer samples. This led us to exclude several of the genes in the region as classical tumor suppressors for sporadic lung cancer. On the other hand, the putative lung cancer TSG in this location may either be inactivated by tumor-acquired promoter hypermethylation or belong to the novel class of haploinsufficient genes that predispose to cancer in a hemizygous (+/-) state but do not show a second mutation in the remaining wild-type allele in the tumor. We discuss the data in the context of novel and classic cancer gene models as applied to lung carcinogenesis. Further functional testing of the critical genes by gene transfer and gene disruption strategies should permit the identification of the putative lung cancer TSG(s), LUCA, Analysis of the approximately 630-kb sequence also provides an opportunity to probe and understand the genomic structure, evolution, and functional organization of this relatively gene-rich region.

Carcinoma, Non-Small-Cell Lung↗

The value of transbronchial lung biopsy in the diagnosis of peripheral lung tumors according to cell type.

BACKGROUND: Transbronchial lung biopsy (TBLB) is a useful diagnostic tool for peripheral lung tumors. However, the success rate is variable. Our study was designed to investigate the value of TBLB without fluoroscopic guidance in the diagnosis of variable cell types of peripheral lung cancers. METHODS: A retrospective study was conducted to investigate a total of 597 patients who had undergone fiberoptic bronchoscopy for lung mass on chest X-ray in Chang Gung Memorial Hospital from January 1996 to December 1998. The lung masses were proven to be malignant by cytology and histology. RESULTS: Of 358 patients (60.0%) proven with malignancy, 107 patients presented with peripheral lung cancer (17.9%), including 59 with adenocarcinoma, 26 with squamous cell carcinoma, 11 with poorly differentiated carcinoma, 3 with small cell carcinoma, and 8 with metastatic cancers. The diagnostic rate of peripheral lung cancer by TBLB reached 54.2%. The sensitivity rates of detection of non-small cell type by TBLB were adenocarcinoma, 50.9%; squamous cell carcinoma, 61.5%; and poorly differentiated carcinoma, 72.7%, while that of small cell carcinoma was 100%. In contrast, the sensitivity rate of TBLB for metastatic cancers was lower (12.5%) than for primary lung cancers. Repeated TBLB of peripheral lung cancers increased the diagnostic rate from 49.5% to 54.2%. CONCLUSION: TBLB is an effective bronchoscopic sampling technique in the diagnosis of peripheral lung tumors without additional risk. The use of TBLB in the clinical routine should be encouraged.

Biopsy, Needle↗

"Shock lung" resulting from perfusion of canine lungs with stored bank blood.

An in situ lung perfusion model was used to study the impact of stored bank blood, with or without dacron wool filtration, on morphologic and functional derangement in canine lungs. Autologous blood was stored 24 hours or 21 days in ACD solution and then passed through standard recipient set filters before perfusion through the left lower lung lobes of dogs equipped to have pressure and gas tensions monitored from pulmonary artery, vein and bronchus. In an additional group of dogs, 21-day stored blood was additionally filtered through dacron-wool prior to lung perfusion. Pulmonary vascular resistance increased markedly for lungs perfused with stored blood, whether or not dacron-wool filtered, as compared with lungs perfused with fresh blood. Effective compliance decreased in both groups of lungs perfused with stored blood, and arteriovenous oxygen gradients decreased significantly in these groups as compared with fresh blood-perfused lungs. As an index of congestion, wet/dry lung weight ratios increased for both groups perfused with stored blood which also showed gross and microscopic evidence of pulmonary edema. As a measure of microaggregated blood debris, screen filtration pressure determinations were not significantly different in fresh or stored canine blood in ACD. We conclude from observations of these canine lung perfusions that pulmonary anatomic and functional injury can result from the use of stored bank blood which may be modified, but not eliminated, by depth filtration. We infer that microaggregated blood debris is not the primary noxious factor in stored canine blood, and a toxic serum-borne factor may be implicated.

Animals↗

Distribution of ventilation in lung transplant recipients: evaluation by dynamic 3He-MRI with lung motion correction.

RATIONALE AND OBJECTIVES: The ability of motion corrected dynamic 3He-magnetic resonance imaging (MRI) to discriminate distributional patterns of inhaled hyperpolarized 3He between different groups of lung transplant recipients was evaluated. METHODS: An ultrafast low-angle shot 2D sequence (temporal resolution 128 ms) was used for ventilation 3He-MRI of 11 single and 6 double lung transplant recipients. After digital motion correction, signal kinetics were evaluated in a tracheal and 7 pulmonary regions of interest. Results from grafts and native lungs as well as from normal and rejected grafts were compared with each other and to reference values from healthy subjects. RESULTS: In emphysema patients, median alveolar rise time, a parameter for increase of alveolar signal, was 0.28 seconds for the graft and 0.48 seconds for the native lung, in fibrosis patients its median was 0.46 seconds for the graft and 0.21 seconds for the native lung. In double lung recipients, alveolar rise time was 0.29 seconds in normal and clinically rejected grafts. CONCLUSIONS: Dynamic ventilation 3He-MRI discriminated normal lung grafts from diseased native lungs in single lung recipients. Graft rejection in double lung recipients could not be discriminated.

Female↗

Immature lung and acute lung injury.

Acute lung injury occurs mostly in the very low birth weight and extremely low birth weight infants. The pathological process leading to acute lung injury includes immature and/or diseased lung that experienced oxidative stress, inflammation and mechanical insult with the bronchial, alveolar and capillary injuries and cell death. It may be the first step to the subsequent development of chronic lung disease of prematurity or bronchopulmonary dysplasia. The mechanisms of lung injury are extensively investigated in the experimental models and clinical studies, mostly performed on the adult patients. At present, the explanations of the mechanism(s) leading to lung tissue injury in tiny premature babies are just derived from these studies. Acute lung injury seems to be rather a syndrome than a well-defined nosological unit and is of multifactorial etiology. The purpose of this review is to discuss the main factors contributing to the development of acute lung injury in the very low or extremely low birth weight infants--lung immaturity, mechanical injury, oxidative stress and inflammation. Nevertheless, numerous other factors may influence the status of immature lung after delivery.

Antioxidants↗

In a canine model, lung preservation at 10 degrees C is superior to that at 4 degrees C. A comparison of two preservation temperatures on lung function and on adenosine triphosphate level measured by phosphorus 31-nuclear magnetic resonance.

Techniques for organ preservation generally use hypothermia to retard metabolic requirements. However, excessive hypothermia may also produce injury. Using a canine left lung allotransplantation procedure, we compared two preservation temperatures (4 degrees and 10 degrees C) in terms of subsequent lung function measured by temporary occlusion of the right pulmonary artery after implantation of the preserved left donor lung. The lungs were flushed with low-potassium dextran electrolyte solution, inflated with 100% oxygen, and preserved for 18 hours. To investigate possible changes of energy stores at different temperatures, we performed phosphorus 31-nuclear magnetic resonance analyses of lung samples. Sequential determinations of adenosine triphosphate levels in lung tissue preserved at 4 degrees, 10 degrees, and 22 degrees C were studied. After transplantation, lungs preserved at 10 degrees C (n = 6) provided significantly better arterial oxygen tension than those preserved at 4 degrees C (n = 6), 451 +/- 46 mm Hg versus 243 +/- 86 mm Hg (p less than 0.05), and lower pulmonary vascular resistance, 581 +/- 68 dynes.sec.cm-5 versus 1006 +/- 157 dynes.sec.cm-5 (p less than 0.05). Adenosine triphosphate levels at 4 degrees and 10 degrees C were stable and did not differ from each other at the end of the 18-hour preservation period: 0.86 +/- 0.04 mumol/gm wet weight for control versus 0.86 +/- 0.07 mumol/gm wet weight for 4 degrees C and 0.93 +/- 0.06 mumol/gm wet weight for 10 degrees C after 18 hours of preservation. Preservation at 22 degrees C caused a 28% depression of adenosine triphosphate after 18 hours of preservation. These results lead us to conclude the following: (1) Optimal temperature for lung preservation is in the vicinity of 10 degrees C, and (2) lung dysfunction caused by excessive hypothermia is not due to a failure to maintain adenosine triphosphate levels. We suspect that adenosine triphosphate is generated by oxidative phosphorylation during lung preservation.

Adenosine Triphosphate↗

Differentiation-dependent expression of I and sialyl I antigens in the developing lung of human embryos and in lung cancers.

The localization of two carbohydrate antigens, I and sialyl I antigens, in the lungs of developing human embryos was investigated using specific monoclonal antibodies and compared with the distribution patterns of the known embryonic antigen, stage-specific embryonic antigen-1 (Lex hapten). When the future bronchi were actively developing from the bronchial buds in the lungs of 50- to 53-day-old embryos, the immature bronchial bud cells were I-, Lex+, while the fully differentiated epithelial cells of the larger bronchus were I+, Lex-. When the bronchiolar bud cells matured into bronchiolar epithelial cells in the lung of a 12-week-old embryo, the immature bronchiolar bud cells were I-,Lex+, while the fully differentiated epithelial cells of the bronchioles were I+,Lex-. Sialylated forms of the antigens finally appeared in the lungs of 18-week-old embryos, when the terminal bud cells actively proliferated and underwent the differentiation process into epithelial cells of alveoli and alveolar ducts. The immature terminal bud cells at this stage were I-, sialyl I-, Lex+, sialyl Lex-i+, while the fully differentiated alveolar epithelial cells were I+, sialyl I+, Lex-, sialyl Lex-i-. After 8 months, the flattened mature alveolar epithelial cells were strongly positive for both I and sialyl I antigens, the strong expression of which continued after birth and even into the adult stage. These distribution patterns indicate that the I and sialyl I antigens are specific markers for the differentiated type cells in each stage of development, while Lex and related embryonic antigens were specific to the immature bud cells in every stage. The above-described differentiation-dependent expression patterns of these antigens seem to be reflected in the distribution of these antigens in human lung cancers, i.e., I and sialyl I antigens were expressed in lung cancer cells more weakly than in normal lung cells, while the Lex and sialyl Lex-i were expressed in cancer cells much more strongly than in normal lung cells. This was further reflected in the serum levels of these antigens in the patients with respiratory disorders. The distribution pattern of the serum levels of these antigens in patients with lung cancers showed sialyl Lex-i greater than sialyl I, indicating that these serum antigens originated from the lung cancer lesion where sialyl Lex-i is much more dominant than sialyl I antigen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Urokinase receptors in lung cancer and normal lung.

Cell membranes from ten non-small cell lung cancers and four specimens of adjacent lung tissue were assessed for the presence of urokinase type plasminogen activator (uPA) receptors. Displacement binding studies using 125I labelled urokinase showed specific binding on lung cancer and lung membrane preparations. Scatchard analysis showed that the dissociation constant of high affinity sites on tumour membranes was 2.9 x 10(-11) M/1 and on lung membranes was 2 x 10(-9) M/1. The concentration of high affinity binding sites on tumour membrane was 54 fmol/mg of membrane protein and on normal lung membrane was 170 fmol/mg protein. Two-point binding assays showed specific binding of urokinase on five of eight tumour membranes and one of three normal lung membranes. There was no correlation between the amount of urokinase bound and tumour subtype or extent of disease. Because of interactions between uPA and epidermal growth factor receptors (EGFr) in cell culture and because lung cancers express increased EGFr we studied the association of uPA receptors and EGFr. Seven tumours expressed EGFr at 6.8-67.6 fmol/mg of protein of EGFr and four normal lung membranes had EGFr at 5.2-15.6 fmol/mg protein EGFr. There was no correlation between uPA receptors and EGFr in this series. We conclude that non-small cell lung cancers carry receptors for urokinase and this provides a novel mechanism for control of local proteolysis.

Adenocarcinoma↗

[Extended hypothermic heart-lung preservation system for cardiopulmonary preservation with retrograde coronary sinus perfusion and lung immersion].

One major restriction of clinical heart-lung transplantation has been the inability to provide extended hypothermic organ preservation. We examined whether core-cooling, retrograde heart perfusion and lung immersion could provide adequate cardiopulmonary preservation. Hence, donor dogs were placed on cardiopulmonary bypass, and rapidly cooled to 15 degrees C. Then heterotopic heart unilateral left lung transplantations were performed. In control group I (n = 5), hearts and lungs were harvested following core-cooling and cardioplegic arrest, and transplanted immediately. In experimental group II (n = 5), heart-lung blocks were similarly excised but stored at 4 degrees C for 12 hours and then transplanted. During preservation, the lungs were immersed in the extracellular solution. For the heart, non-recirculating retrograde coronary sinus perfusion was performed with oxygenated intracellular solution containing perfluorochemicals. Myocardial function determined by the ratio of end-systolic pressure to end-systolic dimension in the experimental group was similar to that in controls. Although pulmonary vascular resistance and extravascular lung water of the experimental group was higher than those in control group, arterial oxygenation was similar in both groups. Thus, extended heart-lung preservation with core-cooling, retrograde heart perfusion and lung immersion technique could be achieved for heart-lung transplantation.

Animals↗

Purification and some properties of a lung-derived growth factor that differentially stimulates the growth of tumor cells metastatic to the lung.

The ability of malignant cells to respond to growth factor(s) present in or secreted by a distant target organ may be important in tumor metastasis. We used metastatic cell lines and clones of the rat 13762NF mammary adenocarcinoma that show reproducible spontaneous metastatic behavior from the mammary fat pad to regional lymph nodes and lung sites. Whereas poorly lung metastatic MTPa and MTC cells did not grow in response to lung-conditioned medium, highly lung-metastatic MTLn3 cells responded and grew rapidly in lung-conditioned medium. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was purified by using hydroxylapatite affinity and anion exchange chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis. The activity in each of the purification fractions was measured by determining their ability to increase the number of MTLn3 cells in serum-deprived culture. The major component that differentially stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of Mr approximately 66,000. Under reducing conditions, its apparent Mr was approximately 72,000. This lung-derived mitogen was stable at pH 4.0-9.0, possessed a pI of 6.9-7.0, and preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in rat 13762NF mammary adenocarcinoma and murine B16 melanoma tumor systems. The activity of porcine lung-derived growth factor was not affected by pretreatment with antisera to porcine insulin, human granulocyte-macrophage colony-stimulating factor, human platelet-derived growth factor, or murine epidermal growth factor. It was inactivated by reduction with dithiothreitol or exposure to high temperature (95 degrees C). The results suggest that specific organ-derived growth factors are important in metastatic colonization and organ growth of particular malignant cells.

Adenocarcinoma↗

Monoclonal antibody that distinguishes small-cell lung cancer from non-small-cell lung cancer.

To examine whether a monoclonal antibody, TFS-4, can distinguish small-cell lung cancer from non-small-cell lung cancers, an extensive survey of fresh lung tumors, cancers from other organs, and normal tissue specimens has been carried out. The antibody has been shown to react specifically with small-cell lung cancer (15 of 15) but not with squamous cell carcinoma (0 of 20), adenocarcinoma (0 of 20) of the lung, or large-cell lung cancer (0 of 2). It reacted neither with other malignancies, including colorectal cancer, gastric cancer, and malignant lymphoma, nor with such normal tissues as trachea, lung, liver, pancreas, colon, kidney, spleen, skin, striated muscle, bone marrow, or peripheral blood cells. Interestingly, the antibody cross-reacted with central nervous tissues. The antigenic determinant on small-cell lung cancer and that on human brain were both heat labile and trypsin sensitive, but resisted treatment with neuraminidase, suggesting that they represent similar peptides. TFS-4 may be of clinical use in the diagnosis of small-cell lung cancer, while the antigen may help investigate the nature and origin of small-cell lung cancer.

Antibodies, Monoclonal↗

Lack of correlation of severity of lung disease with the phosphatidylcholine concentration in fetal lung fluid from premature lambs at 133-136 days gestational age.

Fetal lung fluid was collected following tracheotomy at the time of delivery of 40 premature lambs at 133-136 days gestational age. The concentration of phosphatidylcholine and saturated photophatidylcholine in fetal lung fluid was compared with the severity of lung disease of the lambs as assessed after 3 to 10 h of controlled mechanical ventilation with only peak inspiratory pressures varied to control the PCO2 values. Phosphatidylcholine concentration in fetal lung fluid did not correlate with the peak inspiratory pressures needed to ventilate the lambs, total lung compliance values, or the surfactant phosphatidylcholine pool sizes measured by alveolar wash after sacrifice. The ratio of saturated to total phosphatidylcholine was constant (0.55 +/- 0.02) and independent of concentration of phosphatidylcholine in the fetal lung fluid. The fetal lung fluid contained only about 0.7% of the final surfactant phosphatidylcholine pool released by the lambs to the alveoli after birth. Within a narrow gestational age range characterized by lung disease of widely varying severity, the phosphatidylcholine concentrations in fetal lung fluid were not predictive of the severity of lung disease.

Animals↗

Effect of baseline lung compliance on the subsequent response to positive end-expiratory pressure in ventilated piglets with normal lungs.

OBJECTIVE: To determine the pulmonary function and hemodynamic effects of incremental positive end-expiratory pressure in two groups of normal ventilated newborn piglets with different baseline dynamic lung compliance. DESIGN: Prospective, controlled, intervention study. SETTING: Animal laboratory. INTERVENTIONS: One group of piglets (inflation group) was prepared with 3 cm H2O (0.29 kPa) positive end-expiratory pressure and a maximal lung inflation to increase baseline lung compliance as compared with the other group (no-inflation group), prepared by 3 hrs of ventilation at zero end-expiratory pressure. Both groups were then subjected to a sequence of incremental positive end-expiratory pressures from 0 to 12 cm H2O (0 to 1.18 kPa) in 2-cm increments for 15-min periods at each level followed by a 60-min recovery period at zero end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Pulmonary function, hemodynamic and blood gas data were collected at each positive end-expiratory pressure value and at 15-min intervals during recovery. Baseline dynamic lung compliance was 5.2 +/- 0.3 mL/cm H2O (53.04 +/- 3.06 mL/kPa) in the inflation group and 2.5 +/- 0.1 mL/cm H2O (25.5 +/- 1.02 mL/kPa) in the no-inflation group. No differences were found in any other pulmonary function, hemodynamic or blood gas value at baseline. Incremental positive end-expiratory pressure resulted in a decrease in dynamic lung compliance and an increase in end-expiratory lung volume in both groups of piglets; dynamic lung compliance was greater in the inflation group at all times. No differences were found in end-expiratory lung volume between groups. Hemodynamic changes in both groups of piglets included: decreased cardiac output and increased pulmonary vascular resistance and systemic vascular resistance. The changes in cardiac output (-23% vs. -32%), pulmonary vascular resistance (+53% vs. +95%), and systemic vascular resistance (17% vs. 51%) were less in the inflation group as compared with the no-inflation group. CONCLUSIONS: Baseline dynamic lung compliance is an important determinant of the subsequent effect of positive end-expiratory pressure on pulmonary function and hemodynamics in the ventilated piglet with normal lungs.

Animals↗

Projections for pediatric heart-lung and lung transplantation.

There is limited international experience in heart-lung or lung transplantation in children less than 16 years of age. Although the indications for lung transplantation are quite different in children compared with adults, the indications for heart-lung versus lung transplantation in children are quite similar. These indications consist of end-stage pulmonary disease, such as cystic fibrosis, or end-stage pulmonary vascular disease that is either primary or associated with correctable or corrected congenital heart disease. The results reported in the international registries show little difference in early and intermediate survival between children who underwent transplantation by the heart-lung or the lung techniques. Actuarial survival at 1 year is approximately 70%, with a survival at 2 years of 40% to 50%. These results are probably slightly inferior to the results in adults, even if differences in indications for transplantation are taken into account. Children may be more susceptible to rejection, infection, and viral challenges, the consequences of which may be more significant in pediatric lung transplantation than in pediatric heart transplantation. In addition, lymphoproliferative diseases are more common in children and may be harder to control by decreasing immunosuppressive therapy than in adults. In spite of these caveats, surviving children often have good functional results and a markedly improved quality of life after heart-lung and lung transplantation unless or until severe chronic rejection and obliterative bronchiolitis occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Quantification of CYP2B7, CYP4B1, and CYPOR messenger RNAs in normal human lung and lung tumors.

Cytochrome P450 (CYP) enzymes expressed in human lung can metabolize a variety of xenobiotics, drugs, and endogenous compounds. Metabolism of these substrates may lead to their detoxification or activation and may affect the homeostasis of the lung, its susceptibility to disease, response to therapy, and clinical prognosis. We analyzed the expression of CYP2B7, CYP4B1, and NADPH-cytochrome P450 oxidoreductase (OR) mRNAs in normal lung controls, normal lung from lung cancer patients, and lung tumors using the sensitive technique of RNase protection. The mRNAs of CYP2B7, CYP4B1, and OR were detected in all the normal and a majority of neoplastic tissues. The three mRNAs were quantified and found at an average ratio of 0.89, 4.03, and 0.88% relative to actin mRNA in normal lung, respectively. There was no correlation between the levels of expression of the three mRNAs and the histological diagnosis of tumors. The amounts of each of the three mRNAs varied considerably between patients, but analysis of frequency distribution of the levels of CYP2B7 and CYP4B1 mRNAs did not present evidence for genetic polymorphism as a possible source of the observed interindividual variability. Levels of expression of the two P450 mRNAs were reduced (2.3- and 2.4-fold) in the neoplasms compared to normal lung. The level of OR mRNA expression was uniform with no significant differences between normal and neoplastic tissues, and its interindividual variability was the lowest amongst the three mRNAs studied. All mRNAs had increased interindividual variability in neoplastic tissues. Analysis of the patients' smoking histories and the level of CYP2B7, CYP4B1, and OR mRNAs revealed no evidence for their induction by compounds present in cigarette smoke. This study identifies and characterizes lung and lung tumor mRNAs encoding enzymes that may participate in the metabolism of xenobiotics in humans.

Cytochrome P-450 Enzyme System↗

[Results of 75 lung transplantations performed in Groningen in 1990-1995. Lung Transplantation Group Groningen].

OBJECTIVE: To describe the development of the lung transplantation programme in Groningen, and the results of single and bilateral lung transplantations in the first 75 consecutive patients, up to December 1995. DESIGN: Retrospective. SETTING: Academic Hospital Groningen, the Netherlands. METHODS: The results of the lung transplantation programme were evaluated retrospectively. RESULTS: In November 1990 the first unilateral lung transplantation was performed in Groningen in a patient with pulmonary fibrosis. In February 1991 a national lung transplantation programme for the Netherlands was instituted in Groningen by the government. Of 500 patients referred from all over the Netherlands from 1990 to December 1995, 75 were transplanted, 16 unilaterally and 59 bilaterally. The actuarial survival for all patients was 85% after 1 year and 72% after 2 years. After transplantation 16 patients died (21%) after 15 months follow-up (median). Early mortality (5%) was caused by graft failure, late mortality (16%) by chronic rejection and lymphoproliferative disease. The mean time on the transplantation waiting list was 9.3 months; it increased during the programme. The limiting factor for further expansion of the programme was caused by donor scarcity. The lungs from only 16% of the multiorgan donors reported by Eurotransplant to our centre could be transplanted. CONCLUSION: The results of the lung transplantation programme in Groningen are good but with an increasing number of lung transplantation centres in the Eurotransplant region the further development of lung transplantation in the Netherlands will depend mainly on the availability of lung donors from the Netherlands.

Adolescent↗

Second lung cancers in patients successfully treated for lung cancer.

The rate of developing second lung cancers and other aerodigestive tumors in patients who have been treated for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult smokers. The risk of second lung cancers in patients surviving resection of NSCLC is approximately 1% to 2% per year. The series reported show that the patients who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I and II). The survival of patients after the second resection of lung cancer is similar to that of patients presenting with initial NSCLC. The risk of second lung cancers in patients surviving SCLC is 2% to 14% per patient per year and increases two- to seven-fold with the passage of time from 2 to 10 years. The risk of second lung cancers in patients treated for SCLC appears to be higher than that found in patients with NSCLC who were treated only with surgical resection. In addition, the chances of successful resection of second primary NSCLCs in patients who were treated for SCLC is much less than that for patients with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC who continue to smoke cigarettes increase their rate of developing second lung cancers. The contribution of chest radiation and chemotherapy administration to the risk of developing second lung tumors remain to be defined but may be responsible for some of the increased risk in patients treated for SCLC compared to patients undergoing a surgical resection for NSCLC.

Actuarial Analysis↗