Search

OBJECTIVES: Acute lung injury can result from distinct insults, such as sepsis, ischemia-reperfusion, and ventilator-induced lung injury. Physiologic and morphologic manifestations of disparate forms of injury are often indistinguishable. We sought to demonstrate that acute lung injury resulting from distinct insults may lead to different gene expression profiles. DESIGN: Microarray analysis was used to examine early molecular events in lungs from three rat models of acute lung injury: lipopolysaccharide, hemorrhage shock/resuscitation, and high-volume ventilation. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats (body weight, 300-350 g). INTERVENTIONS: Rats were subjected to hemorrhagic shock or lipopolysaccharide followed by resuscitation or were subjected to sham operation. First hit was followed by ventilation with either low (6 mL/kg) or high (12 mL/kg) tidal volume for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Physiologic and morphologic variables were assessed. Total RNA was hybridized to Affymetrix chips. Bioconductor was used to identify significantly altered genes. Functional enrichment predictions were performed in Gene Ontology Tree Machine. Confirmation studies included real-time polymerase chain reaction, Western blots, and immunohistochemistry. Physiologic and morphologic variables were noncontributory in determining the cause of acute lung injury. In contrast, molecular analysis revealed unique gene expression patterns that characterized exposure to lipopolysaccharide and high-volume ventilation. We used hypergeometric probability to demonstrate that specific functional enrichment groups were regulated by biochemical vs. biophysical factors. Genes stimulated by lipopolysaccharide were involved in metabolism, defense response, immune cell proliferation, differentiation and migration, and cell death. In contrast, high-volume ventilation led to the regulation of genes involved primarily in organogenesis, morphogenesis, cell cycle, proliferation, and differentiation. CONCLUSIONS: These results demonstrate the application of functional genomics to the molecular 'fingerprinting' of acute lung injury and the potential for decoupling biophysical from biochemical injury. [ABSTRACT FROM AUTHOR]

We report a 102-year-old female who underwent surgery for spontaneous pneumothorax. As leakage did not disappear for over one month, she was referred to our hospital for surgery. Video-assisted thoracoscopic surgery was performed. Multiple small bullae were observed, and one of which was the cause of leakage. She was successfully treated by pleural covering with polyglycolic acid sheet and fibrin glue. Patients of such advanced age can be good candidates for surgical treatment of spontaneous pneumothorax, when they have no severe underlying diseases.

A 76-year-old woman with a history of radical mastectomy for cancer of the right breast 38 years previously developed a solitary right lung nodule which was a metastasis from breast cancer. Diagnosis of the cause of a solitary pulmonary nodule is usually difficult in a patient with a history of extrapulmonary malignancy. A solitary pulmonary metastasis from breast cancer with a disease-free interval of longer than 15 years has been quite rarely reported. We describe an unusual case of a solitary pulmonary metastasis from breast cancer 38 years after the initial treatment.

We reviewed 66 cases of traumatic rib fracture by traffic accident between January 2009 and December 2011. The age of patients ranged from 18 to 88 years, with an average age of 55.6, and they were predominantly male. They met with traffic accident when driving automobiles in 30 cases, driving motorcycles in 15 cases, and walking in 9 cases. The average number of fractured ribs was 4.1±3.2.Multiple rib fractures were observed in 75.8% of patients. Injuries other than rib fractures were involved in all patients who suffered over 7 rib fractures. Except one who died of pneumonia 62 days after traffic accident, 7 of 8 patients died within 48 hours:6 in a shock state and 1 in cardiac pulmonary arrest on arrival. About 80 % of the patients with rib fractures were hospitalized. As traffic accidents could cause any type of injuries including rib fractures, it is important to examine the whole body when patients were transported to a hospital.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. To support breathing of some patients with ALS in its severe condition, mechanical ventilation is indispensable. However, mechanical ventilation has been known to induce pneumothorax by the damage of lung cells in response to mechanical stretch. An ALS 50-year-old male on mechanical ventilation was referred to our department for left pneumothorax. After an unsuccessful drainage for a couple of weeks, he underwent a partial resection of the left lung. On 3rd postoperative day (POD) the left lung collapsed again. Moreover, on 6th POD, the right pneumothorax occurred. Regarding the right pneumothorax, drainage was effective with a continuous pressure of -10 cm H2O, and the chest tube was removed soon. An air leak from the left chest tube persisted, and the left lung expansion was not enough with its apex line around the clavicle. On 42nd POD, a drainage pressure was increased up to -15 cm H2O. Then an air leak disappeared, and the lung expansion was obtained. The adjustment of a chest tube drainage pressure seems to be important, especially when a pneumothorax patient on mechanical ventilation is treated.

The living-donor lobar lung transplantation procedure has been developed clinically as an alternative approach for patients considered too ill to await cadaveric transplantation. With this procedure, 2 lobes are implanted in the recipient in place of whole right and left lungs, respectively. However, the shortage of graft volume can be a problem when compared with full-sized cadaveric grafts. In an attempt to solve this problem, we have developed a native lobe-preserving lobar transplant technique using a large animal model. We report a first successful case of a patient undergoing native lobe-preserving lobar lung transplantation for severe pulmonary emphysema.

Chondrosarcoma of rib origin is rare accounting for about 2% of all chondrosarcomas. A 63-year-old female with an anterior chest wall tumor was referred to our institution for surgical treatment of a 2nd chondrosarcoma in the right 2nd rib 4 years after the initial surgery for its primary lesion. Computed tomography (CT) showed a low density mass, 36 mm in diameter, arising from the 2nd rib. An extended excision of the chest wall including the tumor was performed followed by the reconstruction of the chest wall with double Marlex Mesh. As she had already undergone the reconstruction of the chest wall for its primary lesion, this reconstruction was her 2nd one. Nevertheless, her respiratory condition was well preserved with no significant chest deformity. Wide excision and reconstruction could be performed for the 2nd arising chondrosarcoma of the rib even after the initial lesion was already widely removed and reconstructed.

A rare complication of percutaneous endoscopic gastrostomy (PEG) is gastrocolocutaneous fistula which usually occurs after replacement of the PEG tube. As tube feeding is directly delivered to the transverse colon, patients typically present with a sudden onset of transient diarrhea within minutes after PEG tube feeding. A radiographic study using water-soluble contrast material via the PEG tube shows the tip of the tube in the transverse colon. We present here a patient who had this complication after PEG insertion. A PEG tube for enteral feeding was placed in a 27-year-old man with cerebral plasty and a severe scoliosis. After replacement of the PEG tube, he developed diarrhea after each PEG tube feeding. The diagnosis of gastrocolocutaneous fistula was made after injection of gastrografin from the PEG tube. Another gastrostomy tube was placed surgically and the fistula was then also excised. In conclusion, gastrocolocutaneous fistula must be considered as a complication of PEG tube placement when patients with a PEG tube develop a sudden onset of transient diarrhea immediately after PEG tube feeding.

Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural metastasis of lung cancer without pleural effusion, is a condition occurring in T4 lung cancer. Positron emission tomography (PET) has been reported to be useful for the diagnosis and staging of lung cancer. It has been reported that positive findings on PET scans of indeterminate pleural abnormalities at computed tomography (CT) are sensitive to malignancy. We encountered two cases of dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and a small pleural nodule less than 10 mm in size, all of which were positive findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological thoracoscopic diagnosis remains mandatory before planning treatment, our cases may suggest that PET/CT will be useful as a screening modality for dry pleural dissemination of lung cancer.

A 57-year-old man was accidentally hit by concrete blocks weighing 3 tons on his right side, and was admitted to a hospital. The radiologic findings taken immediately after trauma demonstrated pneumo-mediastinum, subcutaneous emphysema with multiple rib fractures and right clavicle fracture. At computed tomography (CT) scan 16 hours after trauma, pneumomediastinum and subcutaneous emphysema turned out to be worsened with an increased bilateral pleural effusion. An emergency thoracotomy revealed no abnormalities of trachea or esophagus, and neither bronchoscopy or esophagogastroscopy, showed injuries anywhere inside. The chest cavities and mediastinum were washed well with 3 liters of saline solution. The patient had a good course after surgery without any complications, and was discharged at the 18th hospital day. Mediastinal drainage by an emergency operation should always be a choice to a patient having a progressively worsening pneumomediastinum which might cause tachycardia, low blood pressure, and severe dyspnea due to compression of blood vessels and trachea.

Pentraxin 3 (PTX3) is an acute-phase protein, which can be produced by a variety of tissue cells at the site of infection or inflammation. It plays an important role in innate immunity in the lung and in mediating acute lung injury. The aim of this study was to determine the effect of mechanical ventilation on PTX3 expression in multiple lung injury models. Male Sprague-Dawley rats were challenged with intravenous injection of lipopolysaccharide (LPS) or hemorrhage followed by resuscitation (HS). The animals were then subjected to either relatively higher (12 ml/kg) or lower (6 ml/kg, positive end-expiratory pressure of 5 cmH(2)O) volume ventilation for 4 h. High-volume ventilation significantly enhanced PTX3 expression in the lung, either alone or in combination with LPS or hemorrhage. A significant increase of PTX3 immunohistochemistry staining in the lung was seen in all injury groups. The PTX3 expression was highly correlated with the severity of lung injury determined by blood gas, lung elastance, and wet-to-dry ratio. To determine the effects of HS, LPS, or injurious ventilation (25 ml/kg) alone on PTX3 expression, another group of rats was studied. Injurious ventilation significantly damaged the lung and increased PTX3 expression. A local expression of PTX3 induced by high-volume ventilation, either alone or in combination with other pathological conditions, suggests that it may be an important mediator in ventilator-induced lung injury.

Acute inflammatory responses are one of the major underlying mechanisms for tissue damage of multiple diseases, such as sepsis and acute lung injury. Inflammatory mediators released from a variety of cells in response to acute inflammations can interact with immune cells, microvascular endothelial cells and other tissue cells, to elicit a series of intracellular signaling reactions where activation of Src protein tyrosine kinase (PTK) family members is involved. Using cellular and molecular approaches and transgenic animals, Src PTK family members have been identified to be essential for the recruitment and activation of monocytes, macrophages, neutrophils and other immune cells. Src PTK family members also play a critical role in the regulation of vascular permeability and inflammatory responses in tissue cells. Importantly, animal studies have demonstrated that small chemical inhibitors for Src PTKs attenuated acute lung injury. Further investigation may lead to the clinical application of these inhibitors as drugs for acute lung injury.

Acute inflammatory responses are one of the major underlying mechanisms for tissue damage of multiple diseases, such as ischemia-reperfusion injury, sepsis, and acute lung injury. By use of cellular and molecular approaches and transgenic animals, Src protein tyrosine kinase (PTK) family members have been identified to be essential for the recruitment and activation of monocytes, macrophages, neutrophils, and other immune cells. Src PTKs also play a critical role in the regulation of vascular permeability and inflammatory responses in tissue cells. Importantly, animal studies have demonstrated that small chemical inhibitors for Src PTKs attenuate tissue injury and improve survival from a variety of pathological conditions related to acute inflammatory responses. Further investigation may lead to the clinical application of these inhibitors as drugs for ischemia-reperfusion injury (such as stroke and myocardial infarction), sepsis, acute lung injury, and multiple organ dysfunction syndrome.

Pentraxin 3 (PTX3) is suggested to play important roles in the innate resistance against pathogens, regulation of inflammatory reactions, and clearance of apoptotic cells. PTX3 is the first long pentraxin identified. Long pentraxin shares a C-terminal pentraxin domain with the classical short pentraxin (C-reactive protein, serum amyloid P), but holds an unrelated N-terminal domain that is unique to the long pentraxin. While the short pentraxin is produced only in the liver, PTX3 is made by diverse types of cells, prominently endothelial cells and macrophage, in response to inflammatory signals. Unlike the short pentraxin, the expression of PTX3 in multiple types of tissue cells implies a mechanism for local amplification of innate resistance at the site of infection and inflammation. PTX3 plasma levels are very low in normal subjects but are rapidly increased by inflammatory conditions resulting from a wide range of diseased states, from infection to autoimmune and degenerative disorders. Critically ill patients show elevated circulating levels of PTX3 which are determined by the severity of the disease. Clinical evidence has demonstrated that the elevated PTX3 levels might be a useful early and sensitive marker for severely ill patients. Further studies will definitely be needed to deepen our understanding of PTX3.

Background: We previously reported that post-mortem heparinization by closed-chest cardiac massage is beneficial in lung transplantation from non-heart-beating donors by preventing formation of microthrombi. In this study, we evaluated the optimal time for post-mortem heparinization in canine lung transplantation from non-heart-beating donors., Methods: Left lung transplantation was performed in 25 weight-matched pairs of mongrel dogs. Donors were killed with an intravenous injection of potassium chloride and left at room temperature for 2 hours. The cadaver donors were assigned randomly to one of five study groups. In Group H0, heparin sodium (1,000 U/kg) was given intravenously before cardiac arrest. In Groups H10, H30, H45 and H60, heparin sodium (1,000 U/kg) was given intravenously 10, 30, 45 and 60 minutes after cardiac arrest, respectively, followed by closed-chest cardiac massage for 2 minutes. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran glucose solution and preserved for 60 minutes. After left lung allotransplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 3 hours. Uni- and multivariate repeat analyses were utilized for statistical assessment., Results: After transplantation, gas exchange was significantly worse in Groups H45 and H60 than in Groups H0, H10 and H30. Thrombin/anti-thrombin III complex concentration during warm ischemia was significantly higher in Groups H30, H45 and H60 than in Groups H0 and H10., Conclusions: The optimal time for post-mortem heparinization in lung transplantation from non-heart-beating donors is approximately 30 minutes after cardiac arrest.

Objective: We recently reported a technique of unilateral double lobar lung transplantation (UDLLT) in a canine model that was associated with satisfactory early pulmonary function. The purpose of the present experimental study was to assess the quality of bronchial healing, complication rates, survival rates and long-term pulmonary function of this new transplantation technique., Methods: Unilateral double lobar lung transplantation was performed in 14 weight-matched pairs of dogs. In recipient animals, two grafts obtained from donor animals were implanted in the right hemithorax after right pneumonectomy. One graft (left graft) was implanted as a right upper lobe in an upside-down position and the other (right graft) was implanted in the natural anatomic position. The immunosuppressed recipients were observed for 3 weeks. Transplanted graft function was assessed under left main pulmonary artery occlusion at 1 and 3 weeks after transplantation., Results: All animals survived the operation. Pulmonary artery kinking (3/14, 21%) and pulmonary venous thrombus (4/14, 29%) were exclusively observed in the graft implanted in the upside-down position. These complications decreased as the number of transplantations increased. Two of the first seven (29%) and five of the last seven recipient dogs (71%) survived for 3 weeks with excellent pulmonary function and good bronchial healing., Conclusions: This procedure was associated with a high complication incidence in the non-anatomically positioned graft. However, a precise surgical technique could decrease these complications. This technically demanding procedure provided excellent pulmonary function and good bronchial healing.

Long pentraxin 3 (PTX3), an acute-phase protein, is a newly clarified mediator for innate immunity and inflammation. As a soluble pattern recognition receptor, it has a nonredundant role in antifungal infection. Overexpression of PTX3 worsens acute lung injury. The lung epithelium is a critical factor in defense against pulmonary pathogens; it is also involved in acute inflammatory responses related to tissue injury. However, very little is known about how PTX3 is regulated in the lung epithelium. In this study, we found that i.v. injection of LPS induced PTX3 expression in rat lung alveolar epithelium. Using human lung cell lines and primary epithelial cells, we found that PTX3 expression was significantly up-regulated by TNF-alpha in a time- and dose-dependent manner, but not by LPS. Pretreatment with either actinomycin D or cycloheximide abolished TNF-alpha-induced PTX3 expression, indicating the requirement for both transcriptional and translational regulation. The TNF-alpha-induced PTX3 expression was blocked by SP600125, a JNK-specific inhibitor, but not by the inhibitors against NF-kappaB, ERKs, or p38 MAPK. Knockdown of either JNK1 or JNK2 with small interfering RNA also significantly reduced the regulated PTX3 expression. Thus, lung epithelial cells appear to be a major local source for PTX3 production, which could be induced in vivo from these cells by LPS or other inflammatory stimuli, and may be an important mediator for host defense and tissue damage. The importance of the JNK pathway for the regulated PTX3 expression may be a potential target for its regulation in the lung.

Objective: Microthrombus formation appears to be one of the major detrimental factors in lung transplantation from non-heart-beating donors. The purpose of this study was to evaluate the effects of postmortem heparinization by closed-chest cardiac massage in a canine model of left single-lung allotransplantation from non-heart-beating donors., Methods: Left lung transplantation was performed in 18 weight-matched pairs of mongrel dogs. Donors were killed with an intravenous injection of potassium chloride and left at room temperature for 2 hours. The cadaveric donors were assigned randomly to one of the three groups. In group 1 (n = 6), no heparin was given as a control. In group 2 (n = 6), heparin sodium (1000 U/kg) was administered intravenously before cardiac arrest. In group 3 (n = 6), heparin sodium (1000 U/kg) was administered intravenously 10 minutes after death, then closed-chest cardiac massage was performed for 2 minutes. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran-glucose solution and preserved for 60 minutes. After left lung transplantation, the right pulmonary artery was ligated, and recipient animals were followed up for 3 hours. Univariate and multivariate repeated analyses were used for statistics., Results: Both groups 2 and 3 had significantly better gas exchange and lower pulmonary vascular resistance than group 1. Changes in thrombin-antithrombin III complex concentration during the warm ischemia indicated that postmortem heparinization suppressed clotting activation in the donor., Conclusions: Postmortem heparinization by cardiac massage is beneficial in lung transplantation from non-heart beating donors by preventing microthrombus formation.