Search PubMed⌕ Search

Biomedical subjects

J E Loyd

Publications and source records attributed to J E Loyd.

At least 55 records · Page 3Linked to original sources

Pulmonary artery adventitial changes and venous involvement in primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is associated with a spectrum of structural changes in the pulmonary arteries: increased medial thickness, eccentric and concentric intimal thickening, obliteration and recanalization of arteries, and appearance of plexiform and dilatation lesions. The purpose of the present study was to further characterize these structural changes with particular emphasis on arterial adventitial thickness and alterations in the walls of the pulmonary veins. In addition, to determine whether the characteristic structural changes of PPH were size related, each was related to external diameter. With quantitative techniques, the pulmonary vasculature of 19 patients with PPH and 7 controls was examined by light microscopy. In all 19 patients, we found a striking increase in adventitial, as well as intimal and medial, thickness in arteries of all sizes when compared with controls (P < 0.05). In addition, we found intimal and adventitial thickening of pulmonary veins < 250 mu in diameter in approximately half of the PPH cases (P < 0.05). The frequency of arterial obliteration, concentric intimal thickening, and recanalization was 16, 18, and 11 of 19 cases, respectively. These changes were most prevalent in arteries less than 200 mu in diameter whereas eccentric intimal thickening and plexiform lesions occurred in 15 and 6 of the patients, respectively, and were most widespread in arteries > 200 mu. We conclude that remodeling of the pulmonary vasculature in PPH routinely includes thickening of the arterial adventitia and frequently also includes changes in the walls of the pulmonary veins. The finding that recanalization occurs predominantly in the smaller arteries whereas eccentric intimal thickening occurs mainly in the larger ones suggests that recanalization should not be considered a consequence of thromboemboli but may also occur at sites of more fibrotic intimal change.

Adolescent↗

Extrapulmonary thoracic disease caused by Blastomyces dermatitidis.

A case of blastomycosis is reported involving the mediastinum and compromising the plexus brachialis. The pathology, pathophysiology, and treatment of this patient and of a previously reported patient are discussed and compared with the characteristics of extrapulmonary thoracic disease caused by histoplasmosis. Because of the favorable response of these patients to prolonged antifungal therapy, blastomycosis should be considered in the differential diagnosis of invasive extrapulmonary thoracic disease.

Adult↗

Single lung transplantation: a temporal look at rejection, infection, and survival.

Single lung transplantation (SLT) has emerged as routine therapy for selected patients with end-stage lung disease. This study examines the incidence of rejection, infection, and survival during the first posttransplant year. Twenty-one patients (12 male, 9 female; mean age 46 +/- 13 years) underwent 23 SLT procedures (12 left, 11 right lung). Indications were pulmonary fibrosis in six, emphysema in seven, primary pulmonary hypertension in three, Eisenmenger's syndrome in one, pulmonary veno-occlusive disease in one, a-1 antitrypsin deficiency in two, CREST syndrome in one, and retransplantation (graft failure and bronchiolitis obliterans) in two. All were maintained on triple immunotherapy. Survival at 1 year was 100%. The five patients with preoperative pulmonary hypertension had normal hemodynamics at follow up. Freedom from event at 1 year was rejection 23 per cent, all infections 6 per cent, viral 40 per cent, bacterial 55 per cent, fungal 74 per cent. At 1 year, cumulative incidence (events/patient-year) was rejection 1.61, all infections 2.18, viral 0.78, bacterial 1.12, fungal 0.28. Two of 21 patients have developed bronchiolitis obliterans at 1 and 2 years posttransplant. SLT provided safe, effective treatment for a wide variety of end-stage lung diseases. Rejection and infection, although common, may be safely treated with resolution.

Actuarial Analysis↗

Postischemic hypoperfusion during unilateral lung reperfusion in vivo.

The incomplete restoration of blood flow during reperfusion may amplify injury by prolonging ischemia; this "no-reflow" has been studied extensively in systemic organs. Our goal was to examine lung blood flow and microvascular function, specifically to determine whether blood flow is altered during lung reperfusion injury in vivo. In a unilateral lung model of ischemia-reperfusion in awake sheep, we measured pulmonary vascular resistance in each lung by radiolabeled microspheres. Measurements were made before 14 h of ischemia and again 4 h after reperfusion. Vascular resistance in the reperfused lung increased 3-fold (9.64 +/- 0.85 to 27.04 +/- 4.73 cm H2O/L/min) during reperfusion. The increase in vascular resistance in the reperfused lung fully accounted for the small increase in overall pulmonary vascular resistance (4.04 +/- 0.26 to 5.52 +/- 0.70 cm H2O/L/min). Microvascular permeability in the reperfused lung increased 52% more than in the contralateral lung, measured by an improved indicator dilution method with additional markers sensitive to surface area (butanediol). We conclude that changes in vascular resistance and microvascular function occur during lung reperfusion injury in vivo. The demonstration that postischemic hypoperfusion occurs during lung reperfusion in vivo suggests possible new avenues of approach to related clinical disorders.

Animals↗

Acute inflammation in a sheep model of unilateral lung ischemia: the role of interleukin-8 recruitment of polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMN) contribute to post-ischemic injury in many organs and in a variety of clinical situations. PMN accumulate in both lungs during unilateral lung ischemia in sheep, but the mechanism has not been defined. In this study, we tested the hypothesis that PMN accumulation is a response to chemotactic signals generated during lung ischemia. Chemotactic activity was measured in a modified Boyden chamber using normal sheep PMN as the responding cells. Increased chemotactic activity was observed in both plasma and lung lymph in a time-dependent manner after ischemia. These data indicate that a chemotactic substance immunoreactive to interleukin-8 antibody is formed as a result of unilateral lung ischemia in sheep in vivo and is a possible mediator of PMN inflammation in this model.

Acute-Phase Reaction↗

An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension.

BACKGROUND: Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium. METHODS: We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls. RESULTS: The 24-hour excretion of 11-dehydro-thromboxane B2 (a stable metabolite of thromboxane A2) was increased in patients with primary pulmonary hypertension and patients with secondary pulmonary hypertension, as compared with normal controls (3224 +/- 482, 5392 +/- 1640, and 1145 +/- 221 pg per milligram of creatinine, respectively; P less than 0.05), whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (a stable metabolite of prostacyclin) was decreased (369 +/- 106, 304 +/- 76, and 644 +/- 124 pg per milligram of creatinine, respectively; P less than 0.05). The rate of excretion of all metabolites in the patients with COPD but no clinical evidence of pulmonary hypertension was similar to that in the normal controls. CONCLUSIONS: An increase in the release of the vasoconstrictor thromboxane A2, suggesting the activation of platelets, occurs in both the primary and secondary forms of pulmonary hypertension. By contrast, the release of prostacyclin is depressed in these patients. Whether the imbalance in the release of these mediators is a cause or a result of pulmonary hypertension is unknown, but it may play a part in the development and maintenance of both forms of the disorder.

6-Ketoprostaglandin F1 alpha↗

Hydrostatic pulmonary edema in sheep. Effects of bronchial artery embolization on the plain chest radiograph.

RATIONALE AND OBJECTIVES: The bronchial circulation may influence pulmonary edema. This study evaluates possible effects of bronchoesophageal artery embolization on the plain film manifestations of hydrostatic pulmonary edema in sheep. METHODS: Anteroposterior and lateral chest radiographs were obtained during the induction of pulmonary edema both before and after embolization of the bronchoesophageal artery in six adult sheep. Interstitial lines and perivascular, segmental bronchial, proximal bronchial, carinal, tracheal, and parenchymal edema were evaluated. RESULTS: Only parenchymal edema was graded consistently. Though edema increased with left atrial pressure before embolization (P < .001), there was no similar change afterward. The embolized animals tended to be more edematous by the first film. CONCLUSION: Rather than any protective effect, bronchoesophageal artery embolization may increase edema. This model may be inappropriate for further investigation of the bronchial circulation in the development of human pulmonary edema.

Animals↗

Single lung transplantation: replacement therapy for end-stage lung disease.

Advances in immunosuppression and operative techniques have allowed single lung transplantation to become a viable treatment option at selected medical centers. We describe eight patients, all from the southeastern United States, who had single lung transplantation at Vanderbilt University Medical Center from March 1990 to June 1991. Their diagnoses represent a diverse set of diseases including idiopathic pulmonary fibrosis, primary pulmonary hypertension, emphysema, and pulmonary veno-occlusive disease. After thorough evaluation, the average waiting period to transplantation was 165 days. The posttransplantation periods were conspicuous for rejection, infection, and other complications. All of these recipients have either returned to an active life or are actively recuperating; this center's first single lung recipient has now survived 15 months. Our initial experience with single lung transplantation is encouraging, yet broader application requires that the paucity of donor organ availability be rectified.

Adult↗

Lung ischemia-reperfusion injury in awake sheep: protection with verapamil.

We caused unilateral lung ischemia-reperfusion injury in awake sheep by simultaneously occluding the left pulmonary artery and left main stem bronchus for 12 h. The occluded left lung was inflated with nitrogen. Reperfusion resulted in an elevation of lung lymph flow from 1.3 to 5.0 ml/15 min and an increase in lymph-to-plsma protein concentration ratios. Reperfusion, but not ischemia alone, caused an increase in wet-to-dry weight ratios in both the reperfused left lung and the contralateral right lung. Granulocytes increased in both lungs during the ischemic period and after reperfusion, and hypoxemia developed after reperfusion. The calcium channel antagonist, verapamil, given just before reperfusion, caused a marked attenuation in the reperfusion-induced changes in the lung lymph variables and wet-to-dry weight ratio. However, verapamil did not affect the hypoxemia or granulocyte sequestration seen after reperfusion. We conclude that reperfusion of ischemic sheep lung results in increased microvascular permeability that can be partially prevented by verapamil.

Animals↗

Pulmonary veno-occlusive disease. Fatal progression of pulmonary hypertension despite steroid-induced remission of interstitial pneumonitis.

This report describes a 28-yr-old patient with pulmonary veno-occlusive disease (PVOD). She presented with pulmonary hypertension, hypoxemia, and interstitial pneumonitis. We report the discordance between the response of her hypoxemia and interstitial pneumonitis, which resolved with corticosteroid therapy, and her progressive pulmonary hypertension, which caused fatal right heart failure. This report emphasizes that the radiographic interstitial shadowing of PVOD may be caused by either (1) an inflammatory interstitial pneumonitis (which may be responsive to anti-inflammatory therapy) or (2) interstitial pulmonary edema, or both.

Adult↗

Inexpensive, air-driven ventricular assist or replacement device for use in MR research.

A simple, inexpensive, non-magnetizable, pulsatile air-driven pump has been devised for use in magnetic resonance environments. The pump has a variable stroke volume and stroke rate, is easily cleaned and sterilized, requires relatively small priming volumes and causes no observable hemolysis when blood is used as the perfusate. This device is usable for phantoms, isolated organs or in situ preparations.

Animals↗

Unilateral radiation pneumonitis in sheep: physiological changes and bronchoalveolar lavage.

Radiation pneumonitis is a life-threatening result of therapeutic thoracic irradiation, yet its mechanisms are poorly understood. We studied the effects of unilateral lung irradiation (3,000 rad) in sheep from the immediate response to the later development of radiation pneumonitis. We defined radiation pneumonitis by its diagnostic clinical feature, radiographic infiltration of the irradiated zone with a straight margin corresponding to the radiation port. The immediate response in the few hours after irradiation was characterized by cough, labored respiration, hypoxemia (arterial PO2 decreased 19 Torr), mild pulmonary hypertension (pulmonary arterial pressure increased 20%), and lymphopenia. Hemodynamics and gas exchange returned to normal by day 2 but became abnormal again before or during radiation pneumonitis at 32 +/- 2 days. Respiratory distress, hypoxemia, and pulmonary hypertension recurred during radiation pneumonitis. Bronchoalveolar lavage during radiation pneumonitis contained increased neutrophils (19 +/- 4%, control = 7%), increased protein (0.27 +/- 0.1 g/dl, control = 0.12 +/- 0.03), and severely impaired ability to lower surface tension. Alveolar macrophages from both lungs during unilateral radiation pneumonitis exhibited impaired generation of superoxide after phorbol myristate (only a 30% increase). Normal control alveolar macrophages increased superoxide production after stimulation greater than 400%. We conclude that unilateral lung irradiation in sheep causes a mild immediate response followed by radiation pneumonitis at 1 mo. Unilateral radiation pneumonitis in this model is associated with ipsilateral neutrophilic alveolitis, increased bronchoalveolar lavage protein, and impaired surfactant function, as well as bilateral functional abnormalities of alveolar macrophages.

Animals↗

Fatal hemoptysis: aortobronchial fistula as a preventable cause of death.

Hemoptysis as a result of leaking aortic aneurysms occurs rarely and has a high fatality rate. A case of chronic hemoptysis resulting from an aortobronchial fistula in a patient with an aortic prosthesis is reported. Hemoptysis, even when chronic, should prompt investigation of the possibility of a leaking graft in patients with prosthetic aortic grafts. Chest x-ray and bronchoscopy usually yield nonspecific findings. Aortography may demonstrate an aortic aneurysm and is the preferred diagnostic procedure; however, an aggressive surgical approach is often necessary.

Adult↗

Endotoxin-induced neutrophilic alveolitis and macrophage chemotaxin production in sheep.

The mechanism(s) responsible for endotoxin-induced pulmonary leukostasis has not yet been elucidated. We studied ten unanesthetized sheep by performing serial bronchoalveolar lavages (BAL) before and after infusing Escherichia coli endotoxin to determine whether or not neutrophils appeared in the airways and whether or not endotoxemia stimulated alveolar macrophages to produce neutrophil chemotactic activity. The absolute number and percentage of neutrophils recoverable by BAL increased significantly at 24 hours after infusion of endotoxin. Alveolar macrophages isolated from the BAL of sheep after endotoxemia produced a substance that is chemotactic for neutrophils, a response that is also maximal 24 hours after endotoxin infusion. We conclude that endotoxemia causes migration of neutrophils into lung air spaces and that this response may result from in vivo production of a chemotactic factor(s) by activated alveolar macrophages.

Animals↗

Mediastinal fibrosis complicating histoplasmosis.

Mediastinal fibrosis, the most serious late complication of remote infection by Histoplasma capsulatum, is a thick, dense fibrotic capsule which surrounds a small mediastinal focus of old caseous adenitis. The fibrotic process may accrue over prolonged periods and extend within the lumina of critical mediastinal structures to produce complete occlusion. We summarized clinical and radiographic data for 71 patients with mediastinal fibrosis; the criteria for inclusion were the clinical demonstration of occlusion of major central airways (trachea or mainstem bronchus) or major vessels (pulmonary arteries or veins) and the absence of other disease processes which might cause such obstruction. We selected 65 patients who met these criteria from the medical literature of the last 40 years and report 6 new cases from our experience. The majority of patients were diagnosed between ages 20 and 40. The most common symptoms included hemoptysis, dyspnea, and cough. An accentuated pulmonic component of the second heart sound, wheezing, and localized murmur were among the physical findings reported. Radiographic abnormalities consisted of mass lesions and atelectasis or infiltrates, but were often nonspecific. Chest radiography was deceptively normal in some patients, even in the presence of major central airway or vascular occlusion, especially when the focus was subcarinal. Computed tomography has particular promise to depict the mediastinal abnormalities in this process. Surgery had minimal therapeutic benefit. Because of incomplete followup, the mortality of 30% in this series surely does not represent the true overall mortality of mediastinal fibrosis.

Adolescent↗