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J E Loyd

Publications and source records attributed to J E Loyd.

At least 73 records · Page 4Linked to original sources
PubMed1988

Thromboxane receptor-mediated bronchial and hemodynamic responses in ovine endotoxemia.

The role of thromboxane A2 in sheep endotoxemia, an animal model of the adult respiratory distress syndrome, was investigated by a combined biochemical and pharmacological approach. Endogenous thromboxane biosynthesis was assessed by gas chromatographic-mass spectrometric analysis of urinary (thromboxane B2, 2,3-dinor-thromboxane B2) and plasma (11-dehydrothromboxane B2) metabolites that demonstrated a significant stimulation by endotoxin. The functional relevance of thromboxane A2 was probed with a specific thromboxane-prostaglandin endoperoxide receptor antagonist, SQ 29548. The antagonist significantly blunted the increase in pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and lymph protein clearance induced by endotoxin. Whereas the reduction in lung compliance caused by endotoxin was abolished, the augmented airway resistance was unaffected. From the simultaneous increase in thromboxane biosynthesis and effects of receptor blockade, it was concluded that thromboxane A2 mediates the early pathophysiological changes of sheep endotoxemia. Thromboxane receptor antagonism may offer a potential therapeutic approach to patients at risk of the adult respiratory distress syndrome.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Heterogeneity of pathologic lesions in familial primary pulmonary hypertension.

We analyzed lung specimens from 23 affected members of 13 families with known familial primary pulmonary hypertension. In this heritable disease, the pathogenetic basis of disease should be distinct within families, and the pathologic lesions should reflect the underlying biologic mechanisms. Two pathologic types of primary pulmonary hypertension have been proposed to exist, "plexogenic" and "thromboembolic." The purpose of this study was to determine the nature and variety of pathologic lesions in families with familial primary pulmonary hypertension and to discover whether the pattern of pathologic lesions found supported the existence of two types of disease. We found marked heterogeneity of pathologic lesions within and among families, including frequent coexistence of thrombotic and plexiform lesions. We conclude that the lesions found in primary pulmonary hypertension are not specific but represent different manifestations of the same pathologic process. Thus, plexiform and thrombotic lesions of the pulmonary arterioles may not arise from distinctly different biologic processes but may simply be different manifestations of the same process. Further insights in primary pulmonary hypertension must come from study of the biologic aspects of the intimal lesion.

Fibrosis↗
PubMed1988

Corticosteroids prevent acute lung dysfunction caused by thoracic irradiation in unanesthetized sheep.

We sought to determine the effect of corticosteroid therapy in a new acute model of oxidant lung injury, thoracic irradiation in awake sheep. Sheep were irradiated with 1,500 rads to the whole chest except for blocking the heart and adjacent ventral lung. Seven experimental sheep were given methylprednisolone (1 g intravenously every 6 h for four doses) and thoracic irradiation; control sheep received only irradiation. In irradiated control sheep, lung lymph flow increased from baseline (7.6 ml/h) to peak at 3 h (13.2), and lung lymph protein clearance increased from 5.1 to 9.7 ml/h. Mean pulmonary artery pressure increased in the irradiated control sheep from 19 to 32.4 cm H2O, whereas the lung lymph thromboxane concentration increased from 0.09 to 6.51 ng/ml at 3 h. Arterial oxygen tension in irradiated control sheep fell gradually from 86 mm Hg at baseline to 65 mm Hg at 8 h. Methylprednisolone administration significantly prevented the increase in lung lymph protein clearance, mean pulmonary artery pressure, and lung lymph thromboxane concentration. Methylprednisolone also prevented the fall in arterial oxygen tension after thoracic irradiation, but did not prevent a further decrease in lymphocytes in blood or lung lymph after radiation. We conclude that corticosteroid therapy prevents most of the acute physiologic changes caused by thoracic irradiation in awake sheep.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Acute effects of thoracic irradiation on lung function and structure in awake sheep.

To investigate the acute physiological and structural changes after lung irradiation, the effects of whole-lung irradiation were investigated in fourteen sheep. Ten sheep were prepared with vascular and chronic lung lymph catheters, then a week later were given 1,500 rad whole-lung radiation and monitored for 2 days. Four sheep were given the same dose of radiation and were killed 4 h later for structural studies. Lung lymph flow increased at 3 h after radiation (14.6 +/- 2.1 ml/h) to twice the base-line flow rate (7.5 +/- 1.3), with a high lymph-to-plasma protein concentration. Pulmonary arterial pressure increased twofold from base line (18 +/- 1.6 cmH2O) at 2 h after radiation (33 +/- 3.8). Cardiac output and systemic pressure in the aorta did not change after lung radiation. Arterial O2 tension decreased from 85 +/- 3 to 59 +/- 4 Torr at 1 day after radiation. Lymphocyte counts in both blood and lung lymph decreased to a nadir by 4 h and remained low. Thromboxane B2 concentration in lung lymph increased from base line (0.07 +/- 0.03 ng/ml) to peak at 3 h after radiation (8.2 +/- 3.7 ng/ml). The structural studies showed numerous damaged lymphocytes in the peripheral lung and bronchial associated lymphoid tissue. Quantitative analysis of the number of granulocytes in peripheral lung showed no significant change (base line 6.2 +/- 0.8 granulocytes/100 alveoli, 4 h = 10.3 +/- 2.3). The most striking change involved lung airways. The epithelial lining of the majority of airways from intrapulmonary bronchus to respiratory bronchiolus revealed damage with the appearance of intracellular and intercellular cell fragments and granules. This new large animal model of acute radiation lung injury can be used to monitor physiological, biochemical, and morphological changes after lung radiation. It is relevant to the investigation of diffuse oxidant lung injury as well as to radiobiology per se.

Animals↗
PubMed1986

Transbronchoscopic needle aspiration in the diagnosis and staging of lung cancer.

We examined the safety and yield of transbronchial needle aspiration (TBNA) in 28 patients who were subsequently proven to have lung cancer. TBNA in 48 sites produced no complications. TBNA was positive for carcinoma in the two patients whose tracheal carinae appeared abnormal on computerized tomography. When the carinae were normal, only one of 13 aspirations was positive for cancer. None of eight paratracheal aspirations was positive. Aspiration of visibly abnormal bronchial bifurcations revealed carcinoma in four of 15 cases. We conclude that TBNA is a safe procedure for the diagnosis and staging of lung cancer, and that the likelihood of positive results is increased by the presence of radiologic and endoscopic abnormalities.

Biopsy, Needle↗
PubMed1986

Effects of inspiratory resistance loading on lung fluid balance in awake sheep.

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.

Airway Obstruction↗
PubMed1986

Hilar adenopathy.

Explore the source record for details and available documents.

Adolescent↗
PubMed1985

MR imaging parameters in the study of lung water. A preliminary study.

The use of magnetic resonance (MR) to evaluate lung water is made difficult by several factors: paucity of proton signal from normal lung, respiratory and cardiac motion, and long relaxation times of lung fluids. To optimize scanning parameters for this use, and to test MR's ability to detect and quantitate regional and temporal variations in signal intensity in hydrostatic pulmonary edema, in vivo experiments were performed with a 0.5 tesla whole body MR imaging device. Human volunteers were studied in prone and supine positions using spin echo technique (TE = 30 msec) with varying TR, and with respiratory and cardiac gating. In addition, sedated, intubated, chronically prepared sheep were paralyzed to control extraneous motion and allow the use of a high frequency ventilator, thereby eliminating respiratory gating. Elevated pulmonary hydrostatic pressure was induced in these sheep by inflation of a left atrial balloon. Relative signal intensity from the lung rises with lengthening TR. Cardiac gating diminishes motion artifact, but masks extravascular water by enhancing signal from slowly flowing blood by an average of 44%. A gravity-dependent gradient of signal intensity predictably shifts in supine and prone positions. The use of longer TRs, respiratory gating, and cardiac gating all proportionally prolong data acquisition times to an objectionable degree. Without the use of gating, a gradual rise in relative signal intensity is seen in the sheep lung following the establishment of elevated hydrostatic pressure in the pulmonary circuit, and is most pronounced in the dependent portion of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Cyclooxygenase inhibition during phorbol-induced granulocyte stimulation in awake sheep.

In vitro, phorbol myristate acetate (PMA) causes sheep granulocytes to release superoxide. Infused into sheep, PMA causes leukopenia, hypoxemia, pulmonary hypertension, and increased flow of protein-rich lung lymph. Lung lymph thromboxane B2 and 6-ketoprostaglandin F1 alpha levels rise markedly after PMA infusion. To see whether cyclooxygenase products of arachidonic acid mediate the lung vascular responses to PMA, we infused 5 micrograms/kg PMA twice in each of six sheep, once in the presence of sodium meclofenamate and once alone. We varied the order of paired experiments and allowed 4-7 days between experiments. Meclofenamate (5 mg/kg loading dose + 3 mg X kg-1 X h-1 infusion) given alone had no effect on base-line variables. Meclofenamate inhibited or delayed the initial pulmonary hypertension and hypoxemia after PMA but exaggerated the later increase in pulmonary arterial pressure; it prevented any increase in thromboxane B2 and 6-ketoprostaglandin F1 alpha after PMA. Meclofenamate did not affect the degree of leukopenia or the severity of the later hypoxemia nor did it prevent accumulation of granulocytes in the lung. Lung lymph flow was higher with meclofenamate + PMA than with PMA alone, but lymph-to-plasma protein concentration ratio was lower, suggesting that the main effect of meclofenamate on lymph production after PMA was related to the degree of pulmonary hypertension. We conclude that the early increase in pulmonary arterial pressure caused by PMA is mediated by a cyclooxygenase product of arachidonic acid, possibly thromboxane A2, but the later pulmonary hypertension and the increase in pulmonary vascular permeability are not the result of cyclooxygenase products.

Animals↗
PubMed1984

Familial primary pulmonary hypertension: clinical patterns.

We recently identified a family with 6 deaths in 2 generations from primary pulmonary hypertension. The disease was undiagnosed in several of them, and the family members, geographically separated, were unaware that there was a familial disease. We hypothesized that familial primary pulmonary hypertension (FPPH) might be labeled as nonfamilial in situations where the family history was incomplete. In order to better define the clinical patterns of transmission of known FPPH, we surveyed as many of the previously reported families as possible (9 of 13) and found 8 new cases in 5 of these families. Looking at all cases, the most important finding was the infrequent expression of the gene within some families and the widely differing frequency of expression among families. The pattern was autosomal dominant with a 2:1 female-to-male ratio. One instance of male-to-male transmission excluded x-linkage of the gene. Survival after onset of symptoms was the same as that reported for nonfamilial primary pulmonary hypertension (PPH). We conclude that many apparently nonfamilial cases of PPH may actually have the same etiology as in FPPH.

Adult↗
PubMed1983

Effects of 100% oxygen on lung vascular function in awake sheep.

The purpose of this study was to define the time course of pulmonary toxicity during continuous breathing of 100% oxygen in adult sheep. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange, and for collection of lung lymph. Tracheostomies allowed accurate delivery of either 100% oxygen, compressed air, or hypoxic gas. Six sheep breathed 100% oxygen for 72-96 h, and four sheep breathed compressed air for 96 h. In addition to hypoxic challenges [fractional concentration of inspired O2 (FIo2) = 0.12], some sheep received prostaglandin H2 (PGH2)-analogue infusions to further assess pulmonary vascular reactivity. Lung lymph and blood chemotactic activity were measured by granulocyte migration in modified Boyden chambers. Postmortem lung water content and light microscopy were used to measure pulmonary edema. All sheep breathing 100% oxygen died between 72 (n = 2) and 96 h (n = 4). Sheep breathing oxygen demonstrated lung toxicity by measurements of 1) a fourfold increase in flow of protein-rich lung lymph, 2) increased alveolar-arterial difference in Po2 (greater than 20 Torr on FIo2 = 0.21) and hypercapnic acidemia, and 3) a mean extravascular lung water/dry lung weight of 5.7 (controls = 3.3), and histological evidence of interstitial and alveolar edema. Chemotactic activity in lung lymph at base line increased eightfold within 72-96 h of oxygen breathing. In sheep breathing oxygen, the hypoxic pressor response decreased by 50% at 48 h, and by 72-96 h there was a total absence of hypoxic vasoconstriction. There was no increase in lung lymph prostacyclin metabolite, and sodium meclofenamate did not restore the pressor response. In sheep breathing compressed air none of these changes in pulmonary vascular reactivity, lymph flow, or chemotactic activity occurred. We conclude that prolonged breathing of pure oxygen causes pulmonary edema by increasing lung vascular permeability and that respiratory failure results from both edema and loss of pulmonary vascular reactivity.

Animals↗
PubMed1983

Septicemia and lung injury.

The results of investigations undertaken by the authors which deal with the functional and structural changes in the lungs resulting from gram-negative bacterial endotoxemia and the mechanisms of these changes are analyzed. The authors emphasize the major roles played by granulocytes and metabolites of arachidonic acid in mediating endotoxin-induced lung injury.

Adult↗