Non-pulmonary Diseases Research Articles

Nitric oxide further attenuates pulmonary hypertension in magnesium-treated piglets.

Persistent pulmonary hypertension of the newborn (PPHN) commonly appears as a complication of several pulmonary and non-pulmonary diseases. The hypoxia possibly inhibits Ca2+ +/- dependent K+ channels, thus resulting in membrane depolarization of pulmonary smooth muscle cells, which leads to the opening of Ca2+ channels and Ca2+ entry, resulting in contraction of the vascular smooth muscle. However, magnesium (Mg2+) is an antagonist of Ca2+. We studied the effect of magnesium sulfate on the treatment of hypoxia-induced pulmonary hypertension and compared to the site of action of nitric oxide (NO). Zero-day-old piglets were used in each experiment. The effects of Mg2+ were tested in each hypoxic, normoxic and hyperoxic states. Once the desired physical state was achieved, Mg2+ was administered at a dose of 100 mg/kg approximately every 10 min. In order to determine the exact mechanism of the Mg2+, Nw-nitro-l-arginine (LNNA), a NO synthase-inhibitor, was administered simultaneously with Mg2+ in some of the experiments. There was a significant correlation between the percent reduction of the pulmonary arterial pressure (PAP) caused by magnesium and the level of oxygen (O2) present in the pulmonary artery. The greatest amount of reduction was seen in the hypoxic condition where the least amount of O2 is found. A further reduction in the PAP was seen when NO was given at the end of the Mg2+ trials. There was no significant reduction seen in the systemic arterial pressure. Inhaled NO further reduced the PAP in piglets already treated with Mg2+.

Increased number of glucocorticoid receptor-β–expressing cells in the airways in fatal asthma

Background: We have recently demonstrated an increased number of glucocorticoid receptor-β (GRβ)–positive cells in steroid-insensitive subjects with severe asthma. Insensitivity to steroids may be a major contributing factor in fatal asthma; however, no such direct evidence has been report previously. Objective: Our aims were to investigate the expression of GRβ immunoreactivity, an endogenous inhibitor of steroid action previously associated with steroid insensitivity, within the airways of patients who died of slow-onset fatal asthma and to compare its expression in patients with emphysema and in nonasthmatic subjects who died of unrelated causes. Sections from airways, both large and small, were obtained from 7 patients who died of asthma, 6 who died from emphysema, and 8 who died from nonpulmonary diseases. Sections from lungs of 6 patients with mild asthma whose lungs were resected for carcinoma were also included as controls. Methods: Tissue samples were processed for immunocytochemistry with a polyclonal antibody to GRβ with use of the avidin-biotin technique and with monoclonal CD3, major basic protein, CD68, and elastase antibodies with the alkaline phosphatase–anti-alkaline phosphatase technique. Sequential immunocytochemistry was performed to phenotype the GRβ immunoreactive cells. Tissue sections from both large (>2 mm) and small (<2 mm) airways were examined. Results: There was a significantly greater number of GRβ immunoreactive cells in fatal asthma compared with emphysema and controls (P < .001 and P < .05, respectively). There was no difference in the expression of GRβ in emphysema compared with controls. GRβ immunoreactivity was also significantly higher in fatal asthma compared with mild asthma. The expression of GRβ in the small airways of patients with severe asthma did not differ significantly from that in the large airways. The majority of GRβ-positive cells were T cells and to a lesser extent eosinophils, macrophages, and neutrophils. Conclusion: The results of this study support the association of GRβ expression with fatal asthma and suggest that alternative anti-inflammatory agents need to be considered in the acute setting for patients who are not responding to steroid therapy. (J Allergy Clin Immunol 2000;106:479-84.)

Reduced expression of the alphabeta T-cell antigen receptor by alveolar T-cells.

A previous study revealed that reduced expression (modulation) of the CD3 antigen is a common characteristic of alveolar T-cells in health and disease. As CD3 molecules are noncovalently bound to T-cell antigen receptors (TCR), it was hypothesized that modulation of TCR was also a feature of alveolar T-cells. To demonstrate this, lymphocytes from bronchoalveolar lavage fluid were stained with an anti-alphabeta TCR antibody and analysed by flow cytometry. The expression of alphabeta TCR by alveolar T-cells was evaluated by calculating mean fluorescence intensity (MFI) and was compared with alphabeta TCR expression by autologous blood T-cells. As anticipated from a previous study, modulation of TCR was observed not only in healthy volunteers but also in patients with pulmonary sarcoidosis, other pulmonary diseases, and nonpulmonary diseases. There were no significant differences in MFI of alveolar T-cells among the study groups. The degree of modulation assessed by the difference of MFI between blood and alveolar T-cells was greater for CD4+ cells than for CD8+ cells owing to the higher MFI of CD4+ blood T-cells. Coculture of alveolar macrophages with blood T-cells in vitro induced partial modulation of TCR. These results demonstrate the ubiquity of modulation of T-cell receptors on alveolar T-cells and suggest, in contrast to a previous report by other investigators that it is caused by some nonantigenic mechanism possibly inherent in the alveolar milieu. The implications of this phenomenon in in vivo immune responses of the lung need to be examined.

Ongoing prospective study of segmentectomy for small lung tumors

Background. Lesser resection for small lung tumors remains an unresolved problem. This study was conducted to see whether this type of operation is acceptable or not. Methods. From 1992 to 1994, 55 patients were enrolled in a multicenter trial of limited surgical resection for peripheral tumors of less than 2 cm diameter. The procedure consisted of segmentectomy with exploration of lymph nodes by examining frozen sections. The operation was modified if the report was positive. The intersegmental plane was identified by keeping the resected segments inflated and the preserved segments collapsed. To divide the plane, stapling or electrocauterization on the edge of the collapsed area was used. In this way the resection line was delivered beyond the burdened segment; this was called extended segmentectomy. Results. There were no perioperative deaths, but there were eight postoperative deaths. In 1 patient who died because of local recurrence, it had been known that the margin to the lesion had been narrow (15 mm); 1 had bilateral intrapulmonary nodules, 1 had nodules in the side that was not operated on, and another succumbed to a second neoplasm of small cell lung cancer 4 years after the first operation. The remaining 4 died of nonpulmonary diseases. Almost all other patients are alive and free from recurrence, except for 1 in whom N2 disease was not detected intraoperatively but was confirmed after the operation. Conclusions. The interim results suggest that extended segmentectomy is applicable in patients with a small peripheral lung cancer. However, a wide margin and aggressive intraoperative pathologic examinations are mandatory.

Cyclical edidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis

To compare the bone-mass effects of calcium supplementation and intermittent cyclic etidronate in patients with established corticosteroid-induced osteoporosis. Eighteen male and 21 female patients who had established corticosteroid-induced osteoporosis and were receiving chronic prednisone therapy (> or = 10 mg/d) were enrolled in a prospective 12-month, open-label study. In addition to continuing prednisone therapy, patients received continuous calcium supplementation 500 mg/d (n = 20) or four cycles of intermittent cyclic etidronate therapy consisting of etidronate 400 mg/d for 14 days followed by calcium 500 mg/d for 76 days (n = 19). Bone mineral density (BMD) of the spine (L1 through L4) and proximal femur (total hip, femoral neck, trochanter, Ward's triangle) was measured by dual-energy x-ray absorptiometry at baseline, 6 months, and 12 months by staff blinded to the treatment. Serum calcium, phosphorus, and alkaline phosphatase were also measured at these times. Treatment with intermittent cyclic etidronate for 12 months resulted in significant increases of 5.7% and 6.8% in BMD of the spine and proximal femur (total hip), respectively (P < 0.02 versus baseline; P < 0.001 versus calcium group). Calcium supplementation alone did not prevent significant losses of 3.4% and 4.1% in BMD at the respective sites (P < 0.02 versus baseline). At the end of the study Z scores reflected significant increases in BMD of the spine and proximal femur (all regions) in the etidronate group (P < 0.01), and significant decreases at the spine, proximal femur, and trochanter in the calcium group (P < 0.01). After 12 months, the difference between the groups was 9.1% (P < 0.01; 95% CI 6.3% to 11.9%) at the spine and 10.9% (P < 0.01; 95% CI 7.8% to 14.1%) at the proximal femur (total hip). Seventeen (89%) of the etidronate-treated patients had increases in BMD of both skeletal sites, whereas only 2 (10%) and 3 (15%) of the calcium-treated patients had positive changes in BMD of the spine and proximal femur (total hip), respectively (P < 0.01). Serum calcium, phosphorus, and alkaline phosphatase levels did not change significantly during the study in either treatment group. Both treatment regimens were well tolerated, with no interactions between prednisone therapy and the study medications. Analyses of response by subgroups (female/male, pulmonary/nonpulmonary indication for prednisone) showed no significant attribute-dependent changes during the 12-month study. At baseline, women had significantly lower BMD of the spine and proximal femur (total hip) (P < 0.01), and patients with pulmonary disease had significantly longer duration of prednisone therapy and cumulative prednisone dose (P < 0.03). Intermittent cyclic etidronate reversed the progressive loss of bone mineral density of the spine and proximal femur in female and male patients with established osteoporosis secondary to chronic corticosteroid (prednisone) therapy for pulmonary and nonpulmonary diseases. Calcium supplementation alone did not prevent or attenuate corticosteroid-induced losses.

Utilidad y limitaciones de la medición del CO2 espirado (capnometría) en pacientes pediátricos en ventilación mecánica

): group 1 was formed by 14 patients under ventilatortreatment with nonpulmonary diseases; gioup 2 included 18 patients with mild lung diseases {FiO? 2 > 0.5). Simultaneously arterial carbon dioxidepressure (PaCO

Comprehensive health evaluation of workers in the ceramics industry.

A cross sectional study on ceramics workers in the Seto area of Japan was conducted to determine whether there are differences in the morbidity pattern and overall health among the working populations employed by different sized companies engaged in the ceramics industry. The study population consisted of 3324 male ceramics workers (age range 40-69) who participated in the Seto occupational health screening programme in 1990. The prevalences of pulmonary diseases (silicosis and tuberculosis) and findings of some nonpulmonary diseases were compared in terms of company size by categories of 1-19, 20-49, 50-99, and 100 or more employees. The values of various screening tests were subjected to principle component analysis to extract factors representing key indices of health state. The average factor scores stratified by company size were used to quantitatively evaluate the comprehensive health level. Both prevalence and multivariate analysis showed that the employees working for smaller companies had overall worse health. The smaller the company, the higher the prevalence and the lower the health scores for silicosis and pulmonary tuberculosis tended to be; significantly increased rates and lower health scores for hypertension, anaemia, and glucosuria among small companies were also found when compared with larger companies. The high morbidity of silicosis and pulmonary tuberculosis in smaller companies contributed most to the decline in the overall health level.

Surgery in Patients on Long-term Steroid Therapy

Increased morbidity after operation has been associated with long-term steroid therapy. To determine the correlation between steroid therapy and such morbidity, the perioperative course of 55 steroid-treated patients was reviewed: 27 had bronchopulmonary disorders (group P) and 28 had non-pulmonary diseases (group NP). There were six (11 per cent) deaths, of which three were steroid related. Among the 13 non-lethal postoperative complications, eight were considered to be steroid related in group P and one in group NP. The duration of steroid therapy was for a median of 24 months (range 1-408 months) in group P and for a median of 6 months (range 1-240 months) in group NP (P less than 0.01). In contrast, the daily dose of hydrocortisone or equivalent before operation was significantly lower in group P, with a median of 0.51 mg kg-1 day-1 (range 0.20-2.56 mg kg-1 day-1) than in group NP, with a median of 1.20 mg kg-1 day-1 (range 0.23-7.38 mg kg-1 day-1) (P less than 0.01). In conclusion, bronchopulmonary disorders requiring a long duration of steroid therapy are associated with a higher risk of steroid-related complications after surgery. A convenient mathematical model is proposed which may allow a preoperative assessment of surgical risk, using steroid dose and duration of treatment.

Mast cells in human lungs.

Mast cells were stained deeply in human lung tissue with acidic toluidine blue to obtain maximum numbers possible in paraffin sections. One hundred high-power fields were counted per section, and mean and median values summarized as mast cells per mm2. Immersion-fixed samples of fresh lung tissue (not bronchi) were taken as controls from seven patients after surgery, and showed mean values of 44.7 mast cells per mm2 after formalin fixation, and 51.9 per mm2 after Carnoy's fixative. Mast cell heterogeneity may explain these differences, but so could random variation between counts. In two patients with extrinsic allergic alveolitis (hypersensitivity pneumonitis), fresh lung tissue from open lung biopsies showed raised values of 90.8 and 101.9 mast cells per mm2, matching the high mast cell counts reported in bronchopulmonary lavage fluid in the condition. Control post-mortem lung tissue from two patients dying of non-pulmonary diseases showed mean values of 26.1 and 50.6 mast cells per mm2. Post-mortem lung tissue from three patients dying of asthma showed very low mean values of 4.7, 5.7, and 5.9 mast cells per mm2. Low mast cell counts due to severe degranulation have been reported before in the bronchi in asthma deaths, but not, to our knowledge, in the lung parenchyma. This finding implies a wider area of mediator release, and helps to explain the severity of the acute attack, and the fatal outcome.

Polarographic activity of denatured serum filtrate and external respiration in acute pneumonia

In order to add new objective data to the existing diagnostic complex of pneumonia and its complications, as well as to monitor the course of treatment and make prognosis of the disease we performed a comprehensive comparative study of patients using polarographic and pneumotachographic methods. We followed up 56 patients with acute pneumonia (men - 36, women - 20), aged 15 to 66 years (mean age - 41 years). Pneumonia in 15 (26,8%) patients was without complications, in 25 (44,6%) it developed against the background of chronic bronchitis, in 5 (8,9%) it was complicated by abscessed; in 4 (7,1%) patients there were acute bronchitis, in 3 (5,4%) bronchocarcinomas and cancer metastases into the lungs were revealed, in 4 (7,2%) acute pneumonia occurred against the background of exacerbation of non-pulmonary somatic diseases. Control group consisted of 21 people aged 16-24 years.

Nitrogen Washout and Mortality

We studied the association between different tests of pulmonary function and subsequent mortality. Subjects were drawn from an epidemiology study of chronic obstructive pulmonary disease. Between 1971 and 1976, 2,539 nonpatient adults had tests of forced expiration, diffusing capacity, and single-breath nitrogen washout. By 1981, 115 of those subjects had died, including 3 from known lung disease. In assessing the relationship between lung function and mortality, the following tests of pulmonary function were examined: forced expiratory volume in one second as a percentage of forced vital capacity, forced expiratory volume divided by height cubed, slope of phase III from the single-breath nitrogen test, closing capacity, diffusing capacity for CO, and the ratio of maximal flow at 75% to that at 25% vital capacity. When adjustments for age and smoking were made, slope of phase III was strongly associated with mortality, even more so than tests of forced expiration. There are two possible explanations for this striking relationship between these observed abnormalities of lung function and subsequent overall mortality (which is largely from nonpulmonary disease): the lungs may serve to protect other systems of the body and therefore poor pulmonary function may contribute to a number of diseases leading to death, or lung function may merely reflect existing disorders in other systems of the body, and the observed association between mortality and pulmonary function is a byproduct of nonpulmonary diseases.

Nitrogen washout and mortality.

We studied the association between different tests of pulmonary function and subsequent mortality. Subjects were drawn from an epidemiology study of chronic obstructive pulmonary disease. Between 1971 and 1976, 2,539 nonpatient adults had tests of forced expiration, diffusing capacity, and single-breath nitrogen washout. By 1981, 115 of those subjects had died, including 3 from known lung disease. In assessing the relationship between lung function and mortality, the following tests of pulmonary function were examined: forced expiratory volume in one second as a percentage of forced vital capacity, forced expiratory volume divided by height cubed, slope of phase III from the single-breath nitrogen test, closing capacity, diffusing capacity for CO, and the ratio of maximal flow at 75% to that at 25% vital capacity. When adjustments for age and smoking were made, slope of phase III was strongly associated with mortality, even more so than tests of forced expiration. There are two possible explanations for this striking relationship between these observed abnormalities of lung function and subsequent overall mortality (which is largely from nonpulmonary disease): the lungs may serve to protect other systems of the body and therefore poor pulmonary function may contribute to a number of diseases leading to death, or lung function may merely reflect existing disorders in other systems of the body, and the observed association between mortality and pulmonary function is a byproduct of nonpulmonary diseases.

Respiratory manifestations of systemic disease

Many nonpulmonary diseases may present with respiratory manifestations or may involve the lungs later in the disease course. The mechanisms by which such involvement occurs are almost as diverse as the diseases themselves and include the following. Hematogenous spread of disease is one of the most common mechanisms of lung involvement, for example, lung involvement by metastatic malignant disease. Cytotoxic factors from another anatomic location may be deposited in the alveolar basement membranes and cause pulmonary damage, for example, pulmonary hemorrhage associated with Goodpasture's syndrome. The pulmonary vasculature may prominently manifest generalized disease, as frequently occurs in Wegener's granulomatosis. Toxins accumulated as a result of disease in another organ system may damage the alveolar capillaries and result in pulmonary edema, as can occur in patients with severe azotemia due to renal failure. Depletion of lung surfactant as a consequence of disease in another organ system may produce alveolar collapse and respiratory failure; a disease that can have this effect is acute pancreatitis. The lungs may be the first organs to exhibit, through unknown mechanisms, underlying systemic diseases such as the collagenoses. Humoral factors released in another anatomic site may cause pulmonary problems; for example, bronchospasm may develop in patients with carcinoid of the intestine as a result of serotonin released by the tumor. Injury to another organ system can produce lung damage by complex mechanisms; an excellent example is the occasional development of neurogenic pulmonary edema in patients with trauma to the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

A clinical evaluation of serum angiotensin converting enzyme in sarcoidosis.

Angiotensin converting enzyme was measured in the serum of 52 patients with sarcoidosis, 67 healthy control subjects and 64 patients with pulmonary and non-pulmonary diseases. The patients with sarcoidosis were classified on clinical grounds as having active or inactive disease. In 26 patients with active sarcoidosis not taking corticosteroids the mean serum ACE was significantly higher than in normal controls (P less than 0 . 001). 73% of these patients had elevated serum ACE. Only two out of 12 (17%) patients with inactive sarcoidosis not taking corticosteroids had elevated serum ACE. Serum ACE was normal in patients taking oral corticosteroids for longer than two weeks. Eighty per cent of patients with active sarcoidosis with radiological evidence of pulmonary parenchymal involvement had an elevated serum ACE compared to 25% in patients with normal chest X-rays and 60% of those with bilateral hilar lymphadenopathy. All sarcoid patients with hypercalcaemia had elevated serum ACE whereas only half of those with normal serum calcium had elevated ACE. In the patients with other thoracic and granulomatous conditions serum ACE was normal or rarely marginally elevated. Serum ACE appears to be of value in the diagnosis of active sarcoidosis.

The Value of Fiberoptic Bronchoscopy in the Management of Pulmonary Collapse

Nineteen fiberoptic bronchoscopic procedures were performed on ten patients for the treatment of pulmonary collapse. All but two patients were being treated for severe, life-threatening nonpulmonary diseases. Thick, tenacious, and, at times, purulent mucous plugs were successfully aspirated from the bronchial passages. Complete to partial radiologic reexpansion of the collapsed pulmonary region was observed following all but one procedure. Significant improvement in blood gas levels was also noticed immediately after the procedure. Bronchoscopic examination in these seriously ill patients did not cause any complications. The therapeutic value of fiberoptic bronchoscopic procedures in patients developing pulmonary collapse due to thick secretions and mucous plugs was demonstrated.

Muscle Metabolism in Patients with Chronic Obstructive Lung Disease and Acute Respiratory Failure

1. The concentration of metabolites in intercostal and quadriceps muscle, and pulmonary function, were studied in twelve patients with chronic obstructive lung disease and acute respiratory failure before, during and after standardized treatment at an intensive care unit. The findings were compared with those obtained in hospitalized patients of comparable age with non-pulmonary diseases. 2. On admission, when the patients had marked hypoxaemia, hypercapnia and acidosis, the concentrations of ATP and creatine phosphate were low in both intercostal and quadriceps muscle, particularly the latter. The lactate concentration was increased in relation to control values but glycogen did not differ significantly. 3. In response to therapy, the Pa,CO2 and the patient's acidosis decreased, the vital capacity increased and lung mechanics improved along with the clinical condition. At the same time there were significant increases in the concentrations of ATP, creatine phosphate and glycogen in intercostal and quadriceps muscles, to values similar to, and for glycogen in excess of, those found in control subjects. Lactate concentration fell significantly during treatment. 4. In view of the low initial muscle concentrations of ATP and creatine phosphate in the patients, it is suggested that dysfunction of the respiratory muscles may be an important component of respiratory failure. Moreover, the concentration of energy-rich compounds in muscle rose significantly as the patients responded to treatment, which emphasizes the importance of adequate nutritional therapy in this disorder.

Spherical and Ovoid Lesions of the Lung

Interest in this subject is attested by pertinent articles in current medical journals. There seem to be valid reasons for this. These include asserted increase in clinical incidence of conditions associated with characteristic x-ray changes, and newer diagnostic methods derived from advancing technology. Also, socio-economic implications may have some role in this respect, namely recent developments illustrate that highly competent diagnostic work-up can be carried out with reasonable safety without having the patient hospitalized. Reports of the 1950s indicated an incidence of 1 to 2 percent of solitary round pulmonary nodules on mass chest x-ray surveys. The typical round or oval x-ray shadow does not in itself identify its underlying pathologic substrate or etiology. Small areas of calcifications in these lesions usually rule out malignant neoplasm, except when the latter develops near the hilar region where it may engulf preexisting small calcified foci. London and Winter reported an unusual case of peripheral solitary round lesion caused by adenocarcinoma of the lung with psammamatous calcifications (Arch Int Med 94:161, 1954). Mass x-ray surveys, with follow-up examinations, revealed that less than 5 percent of these shadows connoted malignant tumor. In contrast, it is well to remember that in a large group of collated clinical cases, malignant lung tumor (primary or metastatic), was observed in 40 percent, with a variety of nonmalignant lesions in 60 percent. The latter comprises a rather high number of granlomatous lesions caused by Histoplasma capsulatum, Coccidioides immitis, other fungi, tubercle bacilli and a small number of pathologic entities due to other causes. Spherical and ovoid lesions may be caused by a great variety of diseases. Among these are benign tumors, such as myoma, hamartoma, chemodectoma, neurofibroma, hibernoma and chondroma. Adult type of chondroma has been listed, according to its composition, under various names, such as chondrohamartoma, chondroadenoma, adenolipofibro osteochondroma, lipochendroadenoma and bronchoma. Weinberger et al aptly comment that although adult type of harmartoma is considered by many experts a late-appearing developmental anomaly, its histogenetic and behavioral characteristics are similar to those of a benign acquired tumor (Ann Thorac Surg 15:67, 1973). Viereck found 60 percent of bronchial adenomas as “coin lesions” (Chirurg 4:309, 1970). There are other entities which may cast round or oval shadow: vascular anomalies (arteriovenous fistula, pulmonary venous varicosities, capillary hemangioma, sclerosing hemangioma, anomalous single left pulmonary vein, aneurysm of an intercostal artery), some instances of Loeffler's syndrome (of parasitic, bacterial, pollen or medicinal origin), ornithosis, primary amyloidosis, gumma, small ectopia of some of the abdominal organs, abscess, infarction, subpleural intrapulmonary lymph node, plasmacytoma and xanthomatous lung lesions. Plasmacytoma may remain histologically and clinically nonmalignant or, for reasons unknown, may assume the characteristics of malignant neoplasm. Spherical lung lesion may be a sequel of nonpenetrating trauma. Interlobar transudate in the horizontal fissure of patients with congestive heart failure may be visualized as a round or oval x-ray shadow (“vanishing” or “evanescent chest tumor”). In the differential diagnosis, it is mandatory to exclude nonpulmonary diseases which may be associated with round or oval shadows in chest x-rays. The seemingly puzzling diagnostic enigma of spherical and ovoid lung lesions can be resolved by due attention to medical history of the patient, possible paraneoplastic symptoms and signs, detection and examination of sentinel lymph nodes, specific laboratory studies, including cytologic examinations, special x-ray work-up, determination of the rate of growth of the lesion, fiberoptic bronchoscopy (biopsy and bronchial brushing), transcutaneous needle biopsy, and exploratory thoracotomy. Availability of modern instruments reduces incidental diagnostic hazards to a minimum and thus permits an aggressive therapeutic attitude. Prompt and accurate diagnosis assures optimal treatment.

Lesion of the lung in rats continuously exposed to two parts per million of nitrogen dioxide.

Rats exposed continuously to 2 ppm ot nitrogen dioxide in air survived their ordinary lifetimes with persistent tachypnoea and usually died of nonpulmonary diseases. Resistance to airflow and dynamic compliance were not different from those in controls. Terminal and respiratory bronchiolar epithelium was affected mainly by a loss of exfoliative activity, reduced blebbing of cytoplasm into the airways, reduction in or loss of cilia, and the appearance of rod-shaped intracytoplasmic crystalloid inclusions. Morphologic evidence suggests that rats exposed to 2 ppm would have reduced cleansing function of the periphery of the lung. Pulmonary tissue was embedded in plastic and sections were cut at 1μ for light microscopy and thinner sections for electron microscopy.

STUDIES ON CARBOHYDRATE AND FAT METABOLISM IN THE LUNG

Normal subjects and patients with heart diseases, chronic pulmonary emphysema and other chronic pulmonary diseases were selected for this study. Samples of blood were taken simultaneously from pulmonary artery (mixed venous blood) and brachial artery (arterial blood) at rest, in anoxic state and under other conditions. Glucose, lactic acid, pyruvic acid, serum lipoprotein index, total serum cholesterol and serum phospholipid were checked up. Cardiac output was also measured by Fick as well as dye dilution methods. Carbohydrate and fat metabolism in the lung was studied from the aspects of the arterio-venous differences of the blood substances stated above, and the differences of values of cardiac output determined by two different methods (Fick and dye) were also studied from the standpoint of O2 consumption in the lung tissue. 1) Ratio of two values of cardiac output determined respectively by Fick method and dye dilution method was higher in the chronic pulmonary diseases than in the non-pulmonary diseases. 2) But there was not statistical significance in the arterio-venous differences of glucose, lactic acid and pyruvic acid at rest in general, including non-pulmonary diseases and pulmonary diseases. 3) In the chronic emphysema lactic acid showed higher concentration in the arterial blood than in the mixed venous blood and glucose had a tendency to show higher concentration in the mixed venous blood. 4) During exercise the concentration of lactic acid was decreased after the passage of the lung, and the concentration of glucose and pyruvic acid showed the same tendency to be decreased. But during IPPB/I using room air and during inhalation of 100% O2 or anoxia test, any significant changes were not observed in the concentrations of these 3 substances. 5) The ratio of coefficients of changes in cardiac output by Fick method and dyedilution method produced by exercise seemed to be higher than the ratio of coefficients of changes produced by the other conditions stated above. 6) Serum lipoprotein index and the concentration of total serum cholesterol were increased after the passage of the lung, and on the contrary they were decreased after the passage of myocardium.

Alternating Positive-Negative Pressures in Mechanical Respiration: (The Cycling Valve Device Employing Air Pressures)

1) The simple portable air pressure device is described which safely produces positive and negative phase pressures (exsufflation with negative pressure) without disturbing the circulatory hemodynamics during the brief periods of therapeutic application. 2) The pressure characteristics in the face mask obtained with this unit are recorded,—during a single cough and during a series of coughs. 3) The rapid expiratory air flows created are sufficiently capable of eliminating the accumulated pulmonary secretions in a variety of pulmonary and nonpulmonary diseases. We are presently applying this form of therapy in a series of patients with bronchiectasis, atelectasis of varied etiology and postoperative retention of pulmonary secretions. 4) A detailed case history is presented of the application of the device in a patient with a large atelectatic-cystic area of lung. Copious expectoration followed a series of “coughs” with the apparatus and a large cystic area was successfully evacuated. 5) Control settings added to the basic unit, to permit the use of wider pressure ranges during both positive-negative phases, are presently being explored for the purposes of resuscitation in general.