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Biomedical subjects

C E Cross

Publications and source records attributed to C E Cross.

At least 109 records · Page 6Linked to original sources

Lung clearance of 99mTc-DTPA aerosol in conscious sheep.

This study was initiated to determine the rate and characteristics of 99mTc-DTPA clearance from the whole lung in a group of 9 sheep. Submicronic aerosol droplets were delivered to unsedated sheep held in a sling-like frame. Best fits for clearance curves to single- and biexponentials were calculated. The monoexponential T50 for the aerosol clearance was 293 min +/- 74 SD. Background correction was found to have a minimal effect (approx. 10%). Biexponential fitting only marginally improved correlations in the 8 healthy sheep, but in one additional animal with clinical evidence of pneumonia, clearance was faster and biexponential fitting was substantially better. These clearance values in conscious sheep are longer than previous findings with 99mTc-DTPA in anesthetized sheep. There appears to be a wide variation of radioaerosol 99mTc-DTPA lung clearances among different species, sheep exhibiting a comparatively prolonged clearance profile.

Administration, Inhalation↗

Approach to the patient with diffuse lung disease.

When evaluating diffuse lung infiltrates, the clinician should place special emphasis on the acuity of symptoms, nonpulmonary complaints and findings, environmental exposures, and risk factors for immunosuppressive diseases. Certain radiographic features, such as the distribution of opacities, hilar adenopathy, Kerley-B lines or pneumothorax, or pulmonary function tests demonstrating air flow limitation also narrow the differential diagnosis. One can direct the subsequent workup based on the narrowed differential diagnosis, the pace of disease, the activity of the ongoing inflammatory-immune process, and the age, overall medical condition, and wishes of the patient. Unless a specific diagnosis (for example, hypersensitivity pneumonitis, the treatment of which is withdrawal of the offending agent) can be made, therapy of noninfectious diffuse lung disease is quite unsatisfactory. Immunosuppressive therapy is indicated to arrest the active inflammatory process with the hope that objective signs of improvement will occur after a 3- to 12-month course. Important areas of basic research in pulmonary fibrosis include cell-cell and cell-matrix interactions in the lung interstitium and delineation of fibroblast biology and cytokine-mediated lung connective tissue pathology. More successful therapies will probably evolve from better understanding of the molecular and cellular biology of the lung fibrogenic process.

Bronchoalveolar Lavage Fluid↗

Measurement of bronchial blood flow with radioactive microspheres in awake sheep.

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Airway blood flow distribution and lung edema after histamine infusion in awake sheep.

The present study was designed to evaluate the distribution of bronchial blood flow to major airways and peripheral lung and to quantitate lung edema during a 2-h histamine infusion (2 micrograms.kg-1.min-1) in unanesthetized sheep. By the use of radioactive microspheres, the blood flow to trachea and to tracheal cartilage, smooth muscle, and mucosa/submucosa was determined along with measurements of blood flow to different sized airway segments and the systemic blood flow to lung parenchyma. Histamine greatly increased blood flow to medium-sized (5- to 10-mm-diam) central airways in which blood flow increased 5-10 times base line, whereas in small (1- to 5-mm-diam) central airways the increase was 10-15 times. Blood flow in tracheal mucosa/submucosa increased six times base line, but in tracheal smooth muscle the increase was only three times base line, and in cartilage it remained at base line. Most of the systemic blood flow to the lung perfuses less than 1-mm-diam peripheral airways, and these airways demonstrated less vasodilation during histamine infusion. Mean blood flow to whole-lung parenchyma (whole lung minus trachea) was only two times base line during histamine infusion. Water content of trachea and main stem bronchi was significantly increased after histamine. Histopathologic findings after histamine infusions included congestion and edema of airways with only minor effects noted in alveoli. We conclude that histamine is a potent and selective vasodilator of bronchial vessels and particularly affects blood flow to central airways and to airway mucosal/submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of dietary vitamin E level on the biochemical response of rat lung to ozone inhalation.

We examined the effects of dietary vitamin E level on rat lung response to ozone (O3) inhalation. In one study, we fed 1-month-old Sprague-Dawley (SD) rats a test diet containing 0 or 50 IU vitamin E/kg for 2 months, and then exposed one-half of the animals from each dietary group to 0.8 ppm (1,568 micrograms/m3) O3 intermittently (8 hours daily) and the other half to room air for 7 days. After O3 exposure, we found significant increases in marker enzyme activities in rat lungs from both dietary groups relative to corresponding air-exposed controls, but the magnitude of increases was greater for the 0 IU than the 50 IU group. In another study, we fed 1-month-old SD rats a test diet containing 10, 50, or 500 IU vitamin E/kg for 2 months and then exposed one-half of the animals from each dietary group to 0.8 ppm (1,568 micrograms/m3) O3 continuously and the other half to room air for 4 days. The O3 exposure increased the metabolic activities in rat lungs from all three dietary groups relative to corresponding air-exposed controls, but the magnitude of increases was greater for the 10 IU than the 50 IU or 500 IU group, and the difference between the 50 IU and 500 IU groups was small. Because a greater increase in lung metabolism after O3 exposure is thought to be associated with a greater tissue injury, the results suggest that an absence of dietary vitamin E exacerbates lung injury from O3 inhalation, while its presence protects from injury. However, the magnitude of this protective effect does not increase proportionately with increased dietary vitamin E supplementation beyond a certain level.

Administration, Inhalation↗

Bronchial blood flow measured by video dilution technique in sheep.

Bronchial blood flow was studied with the video dilution technique (VDT) in seven sheep. All animals were anesthetized (thiamylal and halothane) and ventilated. A videodensitometer and a videotape replay of the fluoroscopic image of dye moving through the common bronchial artery were used to construct dye mass vs. time curves. The areas under the curves were inversely proportional to flow in the bronchoesophageal artery, the site of dye injection. At thoracotomy, an electromagnetic flow probe (EMFP) was placed on the common bronchial artery (the major branch of the bronchoesophageal artery) to measure blood flow changes simultaneously by EMFP and by VDT. These two methods of measurement of blood flow to the airways were compared to validate the use of VDT in this circulation. Common bronchial artery blood flow was increased by injection of radiocontrast dye into the fluoroscopically positioned bronchoesophageal artery catheter causing hyperosmotically induced hyperemia. In 160 simultaneous measurements in five sheep, the percent change in flow as measured by EMFP and VDT correlated closely (r = 0.96). When flow changed because of spontaneous aortic pressure changes or pharmacologic intervention (28 simultaneous measurements in five sheep), the percent change in flow by EMFP and VDT also correlated well (r = 0.98). Bronchial blood flow changes in sheep can be measured accurately using the video dilution technique.

Animals↗

Postirradiation malignant fibrous histiocytoma of the trachea.

A 77-yr-old woman presented with a malignant fibrous histiocytoma (MFH) of the trachea 11 yr after right subtotal thyroidectomy and delivery of 5,400 rads to the neck for infiltrating papillary thyroid carcinoma. The tumor developed in the irradiated area. Postirradiation MFH tends to occur in subcutaneous tissues, and is rare in lung parenchyma or airways.

Aged↗

Oxygen radicals and human disease.

Toxic oxygen free radicals have been implicated as important pathologic mediators in many clinical disorders. We discuss the chemistry of oxygen radical production and the roles of iron and of various antioxidants as well as the diseases that have received active attention in oxy-radical research. Particular attention is focused on cigarette smoke oxidants, ischemia-reperfusion-induced radical production, carcinogenesis, and aging. Such research may well provide a firm foundation for therapeutic breakthroughs.

Aging↗

Clearance of instilled surfactant lipid from the lungs of unanesthetized sheep: lipids are differentially transported by nonlymphatic pathways.

The routes used by the lung to dispose of instilled exogenous surfactant lipid components were examined with the sheep chronic lung lymph fistula preparation. Small vesicles of radiolabeled dipalmitoyl phosphatidylcholine (DPPC) either alone or with radiolabeled cholesterol (CHOL) were instilled intratracheally, and samples of lung lymph and plasma were collected at 60-minute intervals for 12 hours. At any time point, the total amounts of either labeled DPPC or CHOL that appeared in lung lymph were small fractions (less than 0.5%) of their respective amounts in plasma. Labeled DPPC, as DPPC alone or as DPPC/CHOL (2:1 molar ratio), appeared simultaneously in plasma and lymph and displayed the same time course of appearance regardless of vesicle composition. CHOL appearance was also simultaneous in both plasma and lymph, but was distinctly slower than that of DPPC. The time differences noted between the appearance of labeled DPPC and CHOL in lymph and plasma indicate that these two lipid components of the instilled surfactant lipid component vesicles appear to be handled in different fashions during their transport from the lung. Further, the data obtained by sampling lung lymph suggest that the lung interstitial space may not play an active role in the transport of exogenously administered lipid from the lung.

1,2-Dipalmitoylphosphatidylcholine↗

Tropoelastin production and tropoelastin messenger RNA activity. Relationship to copper and elastin cross-linking in chick aorta.

The elastin content of the chick thoracic aorta increases 2--3-fold during the first 3 weeks post-hatching. The deposition of elastin requires the covalent cross-linking of tropoelastin by means of lysine-derived cross-links. This process is sensitive to dietary copper intake, since copper serves as cofactor for lysyl oxidase, the enzyme that catalyses the oxidative deamination of the lysine residues involved in cross-link formation. Disruption of cross-linking alters tissue concentrations of both elastin and tropoelastin and results in a net decrease in aortic elastin content. Autoregulation of tropoelastin synthesis by changes in the pool sizes of elastin or tropoelastin has been suggested as a possible mechanism for the diminished aortic elastin content. Consequently, dietary copper deficiency was induced to study the effect of impaired elastin cross-link formation on tropoelastin synthesis. Elastin in aortae from copper-deficient chicks was only two-thirds to one-half the amount measured in copper-supplemented chicks, whereas copper-deficient concentrations of tropoelastin in aorta were at least 5-fold higher than normal. In spite of these changes, however, increased amounts of tropoelastin, copper deficiency and decreased amounts of elastin did not influence the amounts of functional elastin mRNA in aorta. Likewise, the production of tropoelastin in aorta explants was the same whether the explants were taken from copper-sufficient or -deficient birds. The lower accumulation of elastin in aorta from copper-deficient chicks appeared to be due to extracellular proteolysis, rather than to a decrease in the rate of synthesis. Electrophoresis of aorta extracts, followed by immunological detection of tropoelastin-derived products, indicated degradation products in aortae from copper-deficient birds. In extracts of aortae from copper-sufficient chicks, tropoelastin was not degraded and appeared to be incorporated into elastin without further proteolytic processing.

Animals↗

Penicillamine associated pulmonary hemorrhage.

Penicillamine is the drug of choice in Wilson's disease and a therapeutic alternative in rheumatoid arthritis. Autoimmune complications associated with penicillamine include cases resembling systemic lupus erythematosus and Goodpasture's syndrome. We report a case of diffuse pulmonary hemorrhage associated with prolonged penicillamine use in a patient with Wilson's disease with evidence of circulating immune complexes and complement activation, but without serologic or morphologic evidence of systemic lupus erythematosus, Goodpasture's syndrome or renal disease.

Adult↗

Pancreatic pleuropericardial effusions. Fistulous tracts demonstrated by computed tomography.

Demonstration of the fistulous tract linking pancreatic pseudocysts to the mediastinum and pleural cavity has diagnostic and therapeutic implications. In four cases, pseudocyst drainage through the esophageal and aortic diaphragmatic crus into the mediastinum and pleural cavity was delineated by computed tomography. In two cases, significant pericardial effusions were demonstrated. Computed tomography offers an effective diagnostic method when treatment is dependent on anatomic localization of the disrupted pseudocyst and its intrathoracic drainage tract.

Adult↗

Changes in response to ascorbic acid administered orally to rat pups: lung collagen, elastin and protein synthesis.

Rat pups were supplemented orally with high doses of L-ascorbic acid (AA) or D-isoascorbic acid (IA) throughout suckling. The regulation of AA in the lung and its relationship to collagen and elastin deposition were examined. Based on known responses of smooth muscle cells and fibroblasts in culture to high concentrations of AA, it was hypothesized that a markedly elevated intake of AA should increase net collagen deposition, but decrease net elastin deposition in the neonatal rat lung. In two experiments, groups of rat pups were gavaged daily with AA (in saline), in amounts corresponding to 0.1, 1 or 2% of the total consumed milk solids. As controls, pups were gavaged with IA (2% of the milk solids) or saline. The treatments were initiated 2 d postpartum and continued for 19 or 23 d. Compared to the saline-gavaged pups. AA and IA were elevated (twofold) in serum and lung at d 11, but not at d 25. Urinary excretion represented a major route for elimination of excess AA and IA. With respect to collagen and elastin accumulation, only elastin consistently was altered (10-20% decrease) in groups supplemented with AA or IA at the termination of experiments. The rodent appears to defend against elevation of AA concentration in the lung. Consequently, the putative effects of AA on the net deposition of lung collagen and elastin in vivo are less obvious than effects reported by others from in vitro studies.

Administration, Oral↗

Measurement of bronchial blood flow in the sheep by video dilution technique.

Bronchial blood flow was determined in five adult anaesthetised sheep by the video dilution technique. This is a new fluoroscopic technique for measuring blood flow that requires only arterial catheterisation. Catheters were placed into the broncho-oesophageal artery and ascending aorta from the femoral arteries for contrast injections and subsequent videotape recording. The technique yields bronchial blood flow as a percentage of cardiac output. The average bronchial artery blood flow was 0.6% (SD 0.20%) of cardiac output. In one sheep histamine (90 micrograms) injected directly into the bronchial artery increased bronchial blood flow by a factor of 6 and histamine (90 micrograms) plus methacholine (4.5 micrograms) augmented flow by a factor of 7.5 while leaving cardiac output unchanged. This study confirms the high degree of reactivity of the bronchial circulation and demonstrates the feasibility of using the video dilution technique to investigate the determinants of total bronchial artery blood flow in a stable animal model avoiding thoracotomy.

Animals↗

Deferoxamine injection does not affect bleomycin-induced lung fibrosis in rats.

Bleomycin is an antineoplastic agent that causes a dose-related lung fibrosis that limits its therapeutic effectiveness. It has been proposed that the cellular toxicity and antitumor effects of bleomycin occur by formation of O2-Fe(II)-bleomycin complexes that degrade DNA and release O2- and OH radicals that attack other cellular components. Twice daily injections of the iron chelator deferoxamine were utilized in an attempt to ameliorate bleomycin-induced lung fibrosis. They failed to diminish bleomycin-induced lung inflammation and fibrosis in rats.

Animals↗