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[Continuous positive airway pressure and high-frequency independent lung ventilation in patients with chronic obstructive lung diseases].

The original hypoxemia, hypercapnia, high pulmonary hypertension, high resistance of microcirculation vessels, right volumetric ventricular overload, persistent sub-edema of pulmonary intersticium as well as disparity of ventilation and perfusion between both lungs are the main problems in patients with chronic obstructive disease of the lungs (CODL). Such patients are, as a rule, intolerant to the independent lung collaboration or artificial single-stage ventilation (ASV). Patients with respiratory insufficiency, stages 2 and 3, and with a pronounced impaired type of ventilation have originally a deranged blood gas composition, like hypoxemia or hypercapnia. The application of volume-controllable bi-pulmonary ASV in such patients maintains an adequate gas exchange hemodynamics. However, ASV is accompanied by a significantly reduced gas-exchange function of the single ventilated lung and by essentially worsened intrapulmonary hemodynamics. Therefore, what is needed is to use alternative methods of independent lung ventilation in order to eliminate the gas-exchange impairments and to enable surgical interventions at thoracic organs in such patients (who are intolerant to ASV). A choice of a method and means of oxygen supply to the independent lung is of great importance. The possibility to avoid a high pressure in the airways, while maintaining, simultaneously, an adequate gas exchange, makes the method related with maintaining a constant positive pressure in the airways (CPPA) a priority one in case of CODL patients. The use of constant high-frequency ventilation in the independent lung in patients with obstructive pulmonary lesions does not improve the gas exchange or hemodynamics. Simultaneously, a growing total pulmonary resistance and an increasing pressure in the pulmonary artery are observed. Consequently, the discussed method must not be used for the ventilation support of the independent lung in patients with the obstructive type of the impaired external breathing function.

Blood Gas Analysis↗

Single lung transplantation for emphysema. Lessons learned on the field. The Lung Transplant Group of the Ospedale Maggiore of Milan.

Emphysematous patients that were once treated with double lung transplantation can now also be treated with single lung transplantation. However, single lung transplantation in emphysematous patients presents problems in lung size matching, choice of side to transplant and post-operative assistance. Analysing their own experience of three single lung transplants performed on emphysematous patients, the Authors evaluate the effectiveness of the operation, the results and the difficulties encountered. Single lung transplantation is a good therapeutic option for end-stage emphysematous patients. In these patients right lung transplantation is preferable and the donor organ should be oversized. Positive and expiratory pressure in the native emphysematous lung should be applied with extreme caution.

Adult↗

An evaluation of serum microelement concentrations in lung cancer and matched non-cancer patients to determine the risk of developing lung cancer: a preliminary study.

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.

Adenocarcinoma↗

Cardiac innervation after double lung transplantation. Toronto Lung Transplant Group.

Double lung transplantation has been successfully introduced for patients with end-stage pulmonary disease and preserved cardiac function. An advantage of this operation compared with heart-lung transplantation is retention of the recipient's heart. The operative dissection, however, may lead to interruption of sympathetic and parasympathetic pathways to the heart and consequent denervation of the native heart. The cardiac innervation of seven double lung transplant recipients was investigated by the heart rate response to carotid sinus massage, the Valsalva maneuver, intravenous injection of atropine, and exercise. Five single lung and two heart-lung transplant recipients were studied for comparison. Of the seven double lung transplant recipients, three had abnormal responses to carotid sinus massage, six to the strain phase of the Valsalva maneuver, and five to the release phase of the Valsalva maneuver. Three of six double lung transplant recipients tested had no response to intravenous injection of atropine, and five of seven patients had an abnormal recovery of heart rate after maximal exercise. No patient had a normal response to all interventions, and three patients had responses compatible with complete cardiac denervation. It is concluded that cardiac denervation may occur after double lung transplantation, most likely caused by surgical interruption of sympathetic and parasympathetic pathways during dissection of the recipient's trachea.

Adult↗

Multiple markers for lung cancer diagnosis: validation of models for advanced lung cancer.

Sera from 171 patients with advanced lung cancer, from 110 normals, and from 123 subjects with benign respiratory diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen. Individual markers were studied, and optimal combinations of markers were sought for discriminating lung cancer patients from normals and from patients with benign lung disease. Numerous methods for combining the markers were examined, but the methods of logistic regression and recursive partitioning were finally adopted. The best discrimination rules we could find used only carcinoembryonic antigen (CEA) and total sialic acid (TSA). The performance of these rules was validated on an independent serum panel containing sera from 68 patients with advanced lung cancer, from 40 normals, and from 52 patients with benign respiratory disease. The combination rules based on TSA and CEA performed better than a rule based on CEA alone. Logistic discrimination rules with TSA and CEA that were designed to have 95% specificity achieved 54% sensitivity for discriminating advanced lung cancer from normal controls and 52% sensitivity for discriminating advanced lung cancer from controls with benign disease. Some aspects of clinical applicability are discussed, including planned studies for localized lung cancer and the requirement for further testing in specific clinical settings.

Aged↗

Immunohistochemical and histochemical markers of primary lung cancer, lung metastases, and pleural mesotheliomas.

Sections of primary lung carcinomas, lung metastases, mesotheliomas, and lung metastases of some rare mesenchymal tumors were incubated with different cytokeratin (CK), vimentin, desmin, and tissue polypeptide antigen (TPA) antibodies and with antibodies reactive with different hormones (ACTH, PTH, alpha-HCG, Calcitonin CT), CEA, carcinoma-associated antigen (CA1), secretory component (SC), neuron-specific enolase (NSE), alpha-1-antitrypsin (alpha-1-AT), lysozyme (lyso), and S-100 protein (S 100). CK antibodies derived from a 49 kD (reactive with simple epithelia [SE]) and a 67 kD CK polypeptide fraction (reaction with complex epithelia [CE] were useful differentiation markers for the four major groups of lung carcinomas. In one half of small cell carcinomas a positive reaction with NSE antibodies was found. S 100 and SC were good markers for papillary and bronchioloalveolar adenocarcinomas, whereas CEA was less important because of its reactivity with different types of lung carcinomas. To discern clear cell carcinomas of lung and renal origin a positive reaction with vimentin antibodies (some renal but not lung types) and with CA1 (no renal but all lung types) seemed to be useful. All hormone antibodies were of no importance as markers for difficult differential diagnosis, because positive reactivities were found in cases from every major carcinoma group. In addition, a Ca2+-activated adenosine triphosphatase (ATPase) was found in mesotheliomas but not in papillary adenocarcinomas.

Adenocarcinoma↗

[The results of experimental study of six-hour heart-lung preservation by autoperfusion method--its evaluation of optimal conditions and lung function after preservation].

Up to date, it has been reported that the maintenance of ideal function of the preserved lungs were much more difficult than that of the hearts in heart-lung preservation. In this communication the authors have reported the results of experimental study for optimal conditions for preserving better function of the lungs by autoperfusion method by means of heart-lung preparation using 43 dogs. In this study the conditions of the preservation were fixed as following: perfusing blood temperature 29 degrees C, blood flow 30 ml/kg/min., FiO2 30%, FiCO2 5%, tidal volume 15 ml/kg, ventilation rate 10/min., and PEEP 5 cmH2O. Glucose-Insulin-Potassium (0.03 gm., 0.05 U., 0.02 mEq/kg/hr. respectively) were administered continuously by an infusion pump. The results showed that extravascular lung water contents after 6 hours of preservation was 0.79 (mean) +/- 0.01 (SD), which was increased only 1% over than the control group: 0.78 +/- 0.01. There was no significant difference of static lung compliance in two groups: the preserved group was 0.47 +/- 0.02 ml/gm.cmH2O compared to 0.51 +/- 0.06 in the control group. These results suggest that the autoperfusion method on our preserving conditions seems to be very promising and very effective to keep much better condition of the lungs in heart-lung preservation.

Animals↗

Fibronectin fragments in lung lymph after thrombin-induced lung vascular injury.

Fibronectin is an adhesive glycoprotein found in plasma and lymph as well as between lung endothelial cells and their collagenous basement membranes. Fibronectin is highly sensitive to proteolytic cleavage. We determined if fragments of fibronectin appear in lung lymph in association with increased lung protein clearance after thrombin-induced intravascular coagulation. Thrombin was infused intravenously, (80 units/kg for 30 minutes) into sheep (n = 8) surgically prepared with chronic lung lymph fistulas. Plasma and lymph fibronectin was assayed by electroimmunoassay. Fibronectin fragments were detected using Western blot analysis. After thrombin infusion, lymph flow increased 650% above baseline within 1-2 hours in association with a 35% decline in lymph-to-plasma total protein concentration ratio. This was followed by a second phase (3.5-6 hours) of normalized lymph-to-plasma ratios coupled with sustained elevation of lymph flow. Lung protein clearance remained elevated (p less than 0.10) for 5.5 hours. Plasma fibronectin levels declined slightly over 1-5 hours (zero time = 597 +/- 64 micrograms/ml; 1.5 hours = 478 +/- 59 micrograms/ml) and then increased significantly (p less than 0.05) over 24-48 hours (760 +/- 85 micrograms/ml). The amount of low molecular weight fibronectin fragments in lung lymph increased over the 1.5-6 hours post-thrombin and then declined over 12-48 hours. Thus after thrombin infusion, fragments of fibronectin were usually detected in increased amounts of lung lymph in association with an elevation of lung protein clearance.

Animals↗

[Experimental study on preventive effects of lung metastases using LAK cells induced from various lymphocytes--special references to enhancement of lung metastasis after laparotomy stress].

In 5 week-old female SD rats, ether anesthesia or laparotomy for 30 minutes was done, followed by iv inoculation of 1 x 10(6) MRMT-1 cells. On day 14, number of lung metastatic nodules was examined. Preventive effect of LAK cells on lung metastases was also observed. LAK cells were induced from regional lymph node lymphocytes (LN), thymus cells (TC) and spleen cells (SC) of the rats on day 7 after tumor inoculation by incubation with 1 micrograms/ml of R-IL2 (TGP-3) for 4 days. 1) Lung metastases were noted in 100% after MRMT-1 intravenous inoculation, while number of lung metastatic nodules was reduced after iv administration of LAK cells. 2) When MRMT-1 cells were inoculated intravenously after laparotomy stress for 30 minutes, number of lung metastatic nodules was significantly increased and LAK cells reduced it significantly. 3) When R-IL2 sc administration for 4 days was accompanied, number of lung metastatic nodules was less than that of without R-IL2 substitution. 4) The antitumor effect of LAK cells was the strongest in LN-LAK, while it was the weakest in SC-LAK. In conclusion, usefulness of LAK cells for preventing lung metastases by surgical stress was indicated. This fact suggested that possibility of adoptive immunotherapy using LAK cells might be useful for prevention of lung metastases after laparotomy.

Animals↗

Clinical use of differential lung ventilation in the treatment of asymmetric lung injury: report of a case.

Successful treatment of a 26-year-old male with asymmetric lung injury following a traffic accident is described. The patient was admitted with head injuries, right lung contusion, right pneumothorax, and multiple rib fractures (right 1-9). He developed a left pneumohemothorax and complete atelectasis of the lower lobe of the left lung two days later. Conventional mechanical ventilation with and without positive end-expiratory pressure (PEEP), supplemented by repeated therapeutic bronchoscopy, failed to reexpand the left lung. After 16 days of atelectasis, synchronized differential lung ventilation using a double lumen endobronchial tube connected to two ventilators (Siemens 900C) was instituted. Measurement of the tidal volume and static compliance of each lung showed marked inequality and 9 cm H2O of PEEP was applied selectively to the left lung (zero PEEP to the right) in an attempt to equalize tidal volumes. Evident improvement in blood gases and chest radiograph was obtained within 30 min but weaning back to a single lumen tube required 6 days, and was complicated by further episodes of atelectasis. Complete pulmonary and neurological recovery was obtained, and a normal chest radiograph was documented 3 months later. Differential ventilation proved simple to use, and highly effective in the management of this combination of lung problems.

Adult↗

[The distribution of cefotaxime in serum, lung lymph and lung tissue of sheep].

The levels of cefotaxime (CTX) in serum and lung lymph were compared in awake sheep which were prepared for collection of lung lymph. A single dose of 50 mg/kg of CTX was administered intravenously to sheep. The CTX level in serum or lung lymph reached a peak within 15 minutes after administration and decreased rapidly. The measurable concentration persisted for 240 minutes after administration. Ratios of lung lymph to serum concentration of CTX ranged from 1.0 to 1.2. In addition, the CTX levels in serum, lung lymph and tissue of right lower lobe were compared in anesthetized sheep to which CTX 50 mg/kg were given. Ratios of lung lymph and tissue in right lower lobe to serum concentration of CTX were 0.81 +/- 0.14, 0.06 +/- 0.02, respectively. From above results, CTX was well distributed in lung lymph. The levels of CTX in tissue of right lower lobe were markedly lower than those of lung lymph.

Animals↗

Use of the isolated perfused rat lung in studies on lung lipid metabolism.

A procedure for the use of the isolated perfused rat lung in studies on metabolic regulation has been developed. The procedure, reasonably uncomplicated, yet physiological, maintains the lung so that edema is not observed. The phospholipid content remains normal, and incorporation of [1-(14)C]-palmitate, [2-(14)C]acetate, and [U-(14)C]glucose is linear with time for a minimum of 2 hr. The incorporation of [1-(14)C]-palmitate and [2-(14)C]acetate into the total lung phospholipid fraction and into the phosphatidylcholine and phospatidylethanolamine fractions has been studied. Increasing the concentration of palmitate in the medium from 0.14 to 0.51 mm increased by 60% the incorporation of [1-(14)C]palmitate into the total lung phospholipid fraction at 2 hr. When the palmitate concentration of the medium was 0.14 mm, addition of 0.11 and 0.79 mm oleate to the medium decreased [1-(14)C]palmitate incorporation into the total lung phospholipid fraction at 2 hr by 37 and 49%, respectively. The results suggest that the incorporation of exogenous fatty acids, present in the medium perfusing the lung, into lung phospholipids may depend upon the fatty acid composition of the medium. Known specific acyltransferase activities may be responsible for the ordered incorporation of available fatty acids into lung phospholipids.

Acetates↗

Lung function in diffuse interstitial lung disease of unknown cause.

To examine the role of lung function tests in diagnosis and management of patients with diffuse interstitial lung disease (DILD) we measured total lung capacity (TLC), gas transfer (Tl), lung distensibility and arterial saturation (SaO2) and ventilation during progressive exercise in 24 patients with DILD including 18 with biopsy confirmation. Tl was decreased in all patients, in 21/24 there was progressive hypoxia with exercise, in 12/24 TLC was greater than 80% predicted and in 6/18 lung distensibility was normal. Tl and the change of SaO2 with work output during exercise were highly correlated (r = -0.65, p less than 0.001). In serial studies, the change of SaO2 with work output altered most with clinical improvement or deterioration. The clinical course and response to treatment was not related to a particular pattern of abnormal function. These results and those of previous studies indicate that in DILD the most sensitive index of abnormal parenchymal function is Tl, that lung volumes and distensibility may be normal so that the term "restrictive lung disease" can be misleading, that the fall of SaO2 with work output and Tl are the most sensitive parameters for assessing severity and following the course of the disease and that lung function alone does not predict outcome.

Adult↗

Macrophage inflammatory protein-1 alpha mediates lung leukocyte recruitment, lung capillary leak, and early mortality in murine endotoxemia.

Systemic exposure to LPS initiates a complex sequence of events resulting in organ-specific leukocyte recruitment and end-organ injury. We hypothesized that macrophage inflammatory protein-1 alpha (MIP-1 alpha), a C-C chemokine with leukocyte chemotactic and activating properties, may play an important role in lung inflammatory cell recruitment, subsequent lung injury, and mortality in endotoxemia. CD-1 mice were challenged with LPS (200 micrograms), resulting in a maximal 3.5-fold increase in neutrophils (polymorphonuclear leukocytes (PMNs)) at 6 h post-LPS, and a 2.6-fold increase in numbers of macrophages (M phi) within lung minces at 24 h. A time-dependent increase in MIP-1 alpha mRNA and protein was detected in lung after LPS treatment, with immunolocalization of MIP-1 alpha to blood and lung M phi, and the subendothelium. The pretreatment of mice with rabbit anti-MIP-1 alpha Ab resulted in a decrease in the influx of PMNs at 6 h, and influx of M phi at 24 h post-LPS challenge, an approximately 65% reduction in LPS-induced lung permeability to Evans blue, and a modest decrease in mortality at 24, but not 48 h post-LPS. Furthermore, passive immunization of mice with anti-MIP-1 alpha serum resulted in a 35% reduction in ICAM-1 mRNA levels within lung homogenates post-LPS. Finally, the pretreatment of animals with sTNFR:Fc (soluble TNF receptor:Ig construct) resulted in a 60% reduction in LPS-induced MIP-1 alpha mRNA expression within lung homogenates at 4 h post-LPS. Our studies indicate that MIP-1 alpha plays an integral role as a mediator of both PMN and M phi recruitment in murine endotoxemia.

Animals↗

[Lung surfactant: its application to the lung in asphyxia].

This study is a research of the lung in the hypoxic or anoxic state. The examination of lung were performed by light and electron microscopy with the immunohistochemical methods and biochemical analysis of the lung lavage, not only for the morphological appearance of the surfactant but also the changes of its localization and secretion. For the circumstance of hypoxic or anoxic state, gases of carbon dioxide, methane, carbon monoxide and freon were prepared regulating their contents with a fluorometer. In the first stage of the examination, the lung of a rat inhaled the air containing 5% of oxygen showed the so-called tubular myelin which is a lattice-like structure. And this structure was very much like those found in the alveolar space of a new born rat which is lamellar and lattice-like structure coming loosened to a monolayer. This structure is regarded as the morphological expression of the excreted lung surfactant. The appearance of the tubular myelin was observed in the hypoxic state prepared by the gases stated above. By the examination of the lung lavage of rats inhaled the hypoxic air, the contents of phospholipid and protein were showed 2 and 5 times more than those of control rats, respectively. In the human lung which was collected from the dead body diagnosed the cause of death was asphyxia, the tubular myelin was found by the electron microscopy in some cases of the strangulation of the neck, and the immunohistochemical reaction products were also observed by using the anti-human lung surfactant apoprotein mouse antibody, PE10 of SP-A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Postoperative pulmonary tissue changes after autogenous lung and artificial lung bypass].

The changes in autogenous lung oxygenation and artificial lung during cardiopulmonary bypass (CPB) were compared. The results of our investigation showed that autogenous lung oxygenation is less injurious to the lung than bubble oxygenation and is more physiological. We think that during autogenous lung bypass and open heart surgery, the lung is functioning physiologically and is supplied with normal amount of oxygen, while using bubble oxygenation for CPB the native lung is the only nonperfused organ and lung function being insulted by pulmonary ischemia which is one of the most important reason for pulmonary injury after CPB.

Animals↗

Detection of trisomy 7 in nonmalignant bronchial epithelium from lung cancer patients and individuals at risk for lung cancer.

Early identification and subsequent intervention are needed to decrease the high mortality rate associated with lung cancer. The examination of bronchial epithelium for genetic changes could be a valuable approach to identify individuals at greatest risk. The purpose of this investigation was to assay cells recovered from nonmalignant bronchial epithelium by fluorescence in situ hybridization for trisomy of chromosome 7, an alteration common in non-small cell lung cancer. Bronchial epithelium was collected during bronchoscopy from 16 cigarette smokers undergoing clinical evaluation for possible lung cancer and from seven individuals with a prior history of underground uranium mining. Normal bronchial epithelium was obtained from individuals without a prior history of smoking (never smokers). Bronchial cells were collected from a segmental bronchus in up to four different lung lobes for cytology and tissue culture. Twelve of 16 smokers were diagnosed with lung cancer. Cytological changes found in bronchial epithelium included squamous metaplasia, hyperplasia, and atypical glandular cells. These changes were present in 33, 12, and 47% of sites from lung cancer patients, smokers, and former uranium miners, respectively. Less than 10% of cells recovered from the diagnostic brush had cytological changes, and in several cases, these changes were present within different lobes from the same patient. Background frequencies for trisomy 7 were 1.4 +/- 0.3% in bronchial epithelial cells from never smokers. Eighteen of 42 bronchial sites from lung cancer patients showed significantly elevated frequencies of trisomy 7 compared to never smoker controls. Six of the sites positive for trisomy 7 also contained cytological abnormalities. Trisomy 7 was found in six of seven patients diagnosed with squamous cell carcinoma, one of one patient with adenosquamous cell carcinoma, but in only one of four patients with adenocarcinoma. A significant increase in trisomy 7 frequency was detected in cytologically normal bronchial epithelium collected from four sites in one cancer-free smoker, whereas epithelium from the other smokers did not contain this chromosome abnormality. Finally, trisomy 7 was observed in almost half of the former uranium miners; three of seven sites positive for trisomy 7 also exhibited hyperplasia. Two of the former uranium miners who were positive for trisomy 7 developed squamous cell carcinoma 2 years after collection of bronchial cells. To determine whether the increased frequency of trisomy 7 reflects generalized aneuploidy or specific chromosomal duplication, a subgroup of samples was evaluated for trisomy of chromosome 2; the frequency was not elevated in any of the cases as compared with controls. The studies described in this report are the first to detect and quantify the presence of trisomy 7 in subjects at risk for lung cancer. These results also demonstrate the ability to detect genetic changes in cytologically normal cells, suggesting that molecular analyses may enhance the power for detecting premalignant changes in bronchial epithelium in high-risk individuals.

Aged↗

[The effects of surfactant-TA on bleomycin-induced lung injury and lung fibroblast proliferation].

We investigated whether artificial surfactant modified pulmonary fibrosis following the intratracheal administration of bleomycin (BLM 3.75 mg/kg) in rats. Twenty-four hours after the administration of bleomycin, the lungs were washed twice with surfactant-TA (S-TA, 1 mg/ml, 6 ml x 2 times), and replaced with 0.5 ml of 10 mg/ml S-TA. Fourteen days later the animals were sacrificed and the lungs were assayed for collagen content and pathologic changes. BLM-treated rats showed both increases in wet lung weights and lung collagen content, and a loss in body weights (due to lung injury and fibrosis), but these changes were significantly inhibited by the intratracheal administration of S-TA. In vitro studies demonstrated that S-TA inhibited lung fibroblast proliferation in a dose dependent manner (0.01-0.5 mg/ml). This inhibition was also seen in native rat lung surfactant and its protein and lipid components. However, S-TA, did not change the number of rat type II pneumocutes in culture, and likely protected type II cells from dedifferentiation. S-TA inhibited BLM-induced pulmonary fibrosis, probably by directly inhibiting lung fibroblast proliferation.

Animals↗