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Biomedical subjects

J E Heffner

Publications and source records attributed to J E Heffner.

At least 73 records · Page 4Linked to original sources

Platelet prevention of oxidant lung oedema is not mediated through scavenging of hydrogen peroxide.

Previous studies have shown that washed human platelets attenuate oxidant oedema in isolated perfused rabbit lungs through mechanisms dependent on platelet glutathione. We hypothesized that the platelet glutathione redox cycle scavenges hydrogen peroxide in this model and thereby protects vascular endothelial cells from oxidant injury. This hypothesis was tested by asking two questions: (1) do glutathione-supplemented platelets demonstrate augmented lung protection compared with control platelets, and (2) does conjugation of platelet glutathione with 1-chloro-2,4-dinitrobenzene or inactivation of catalase with 3-amino-1,2,4-triazole decrease in vitro platelet metabolism of hydrogen peroxide? We incubated washed human platelets with reduced glutathione or glutathione monoester and observed platelet glutathione contents of 181% and 189%, respectively, compared with control values. Incubation of platelets with N-acetylcysteine did not alter platelet glutathione content. Infusion of glutathione-supplemented platelets into isolated lungs injured by purine and xanthine oxidase did not augment platelet protection compared with untreated platelets. We also found that conjugation of platelet glutathione and/or inactivation of platelet catalase did not decrease the rate constant for platelet metabolism of hydrogen peroxide. We conclude that platelets attenuate oxidant lung oedema through glutathione-dependent mechanisms other than direct scavenging of hydrogen peroxide.

Amitrole↗

Bowel infarction as the initial manifestation of disseminated aspergillosis.

Disseminated aspergillosis in the immunocompromised patient most commonly presents with clinically apparent pulmonary involvement and roentgenographic infiltrates. We report a patient with acute myelogenous leukemia who developed bowel infarction due to gastrointestinal invasion of Aspergillus fumigatus as the initial manifestation of widespread fungal disease.

Adult↗

Vascular erosion by central venous catheters. Clinical features and outcome.

We evaluated the clinical characteristics of eight patients who presented with vascular erosion from central venous catheters and reviewed the available literature. Patients typically presented with dyspnea or chest pain, unilateral or bilateral pleural effusions, and mediastinal widening one to seven days after catheter insertion. Pleural fluid appeared transudative with variable glucose concentrations (range, 174 to 588 mg/dl) that were always greater than concurrent serum values. Diagnosis was delayed 3.0 +/- 1.5 days (range, 0 to 11 days) after vascular erosion. One patient died and four patients received chest tubes. Seven of eight patients had left-sided line placement; six of these seven left-sided catheters abutted the superior vena cava wall within approximately 45 degrees of perpendicular. Results of a literature search confirm the hazards of delayed diagnosis and the importance of left-sided catheter placement as a risk factor for vascular erosion.

Brachiocephalic Veins↗

Diagnostic value of pleural fluid cytology in occult Boerhaave's syndrome.

When Boerhaave's syndrome presents with atypical clinical features and eludes prompt diagnosis, delays in surgical therapy increase complications and mortality. We present a patient with occult Boerhaave's syndrome who had nondiagnostic esophageal contrast studies and thoracic computed tomography. Pleural fluid cytologic analysis established the presence of esophageal rupture by detecting undigested food particles.

Esophageal Diseases↗

Positive pressure mechanical ventilation augments left ventricular function in acute mitral regurgitation.

Although inconclusively established, positive pressure ventilation may augment cardiac function in congestive cardiomyopathies. We report a patient with acute mitral regurgitation who experienced enhanced myocardial performance and resolution of large pulmonary artery v waves during mechanical ventilation. This observation supports the existence of a cardiac booster effect from positive pressure ventilation.

Acute Disease↗

Pleural disease in pregnancy.

Pleural effusions, pneumomediastinum, and pneumothorax are known complications of pregnancy. Although reported in small series and anecdotal case reports, the serious nature of these complications and the potential for misdiagnosis during the events of labor and delivery warrant a careful review of the available literature. In this article the incidence, clinical manifestations, and, where appropriate, therapeutic options of these disorders are discussed.

Antibodies, Antiphospholipid↗

Atrial natriuretic peptide inhibits oxidant-induced increases in endothelial permeability.

Chemically and enzymatically generated oxidants alter endothelial cell shape, increase macromolecular permeability across endothelial cell monolayers, and increase lung microvascular permeability. We examined the effect of ANP (atrial natriuretic peptide) on oxidant-induced injuries to bovine aortic endothelial cell monolayers and to isolated, perfused rabbit lungs. Treatment of cultured endothelial monolayers with glucose oxidase (1.4 U/ml) caused changes in cell shape characterized by a retraction of cells and the formation of numerous intercellular gaps. Glucose oxidase treatment also caused a reduction in F-actin stress fibers visualized by rhodamine-phalloidin fluorescence. Pretreatment (5 min) of the endothelial monolayers with ANP (10(-7) M) attenuated the oxidant-induced changes in cell shape and reduction in F-actin staining. In addition, ANP significantly (P less than 0.05) reduced increases in endothelial monolayer permeability to albumin resulting from glucose oxidase treatment. Oxidant-induced injury of isolated, perfused rabbit lungs produced pulmonary edema measured as an increase in lung weight. This increase in weight was significantly (P less than 0.05) inhibited by pretreatment of lungs with ANP (10(-7) M). Collectively, these results suggest that ANP may act to preserve endothelial barrier function and reduce edema formation caused by oxidant injury.

Animals↗

Washed human platelets prevent ischemia-reperfusion edema in isolated rabbit lungs.

Washed human platelets prevent edema formation in isolated rabbit lungs infused with xanthine oxidase, an enzyme that injures endothelial membranes by generating extracellular oxidants. We hypothesized that platelets would similarly preserve membrane permeability in isolated lungs exposed to ischemia-reperfusion injury, a model that perturbs endothelial cells by the generation of intracellular oxidants. Isolated perfused rabbit lungs (IPL) were exposed to warm ischemia-reperfusion to cause lung edema. The infusion of washed human platelets (1.05 +/- 0.02 x 10(10) cells) prevented edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, histological edema, and preservation of paraendothelial cell tight junctions. Inhibition of the platelet glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, dehydroepiandrosterone, or 1-chloro-2,4-dinitrobenzene interfered with platelet protective effects. In contrast, inhibition of platelet catalase with aminotriazole and H2O2 had no effect on platelet protection. Lung tissue malonyldialdehyde concentrations were similar in isolated lungs exposed to ischemia-reperfusion with or without the infusion of platelets. These results indicate that platelet attenuation of ischemia-reperfusion lung edema depends on platelet glutathione redox cycle antioxidants but not platelet catalase.

Animals↗

Eugenol causes oxidant-mediated edema in isolated perfused rabbit lungs.

Eugenol, an extract of cloves, has been associated with pulmonary edema when inhaled from commercially available clove cigarettes. We tested the hypothesis that eugenol directly causes lung edema through oxidant-mediated mechanisms by infusing eugenol (0.1 and 1.0 mM) into isolated rabbit lungs perfused with a cell-free albumin and physiologic salt solution. We observed lung edema (1.0 mM) as demonstrated by increased lung weight gain and wet-to-dry lung weight ratios without alterations in mean pulmonary artery pressure. The oxygen metabolite scavengers catalase (1,000 U/ml) and dimethylthiourea (30 mM) attenuated lung edema. Instillation of dimethylurea, superoxide dismutase, or heat-inactivated catalase did not prevent lung edema formation. We conclude that eugenol causes lung edema in isolated lungs through oxidant-mediated mechanisms in the absence of circulating formed blood elements. Eugenol may be a valuable compound in the laboratory investigation of edemogenic disorders.

Animals↗

Renal vein thrombosis. Initial manifestation of Goodpasture's syndrome.

We report a patient who presented with renal vein thrombosis and nephrosis that progressed to alveolar hemorrhage and renal failure. Renal biopsy immunofluorescence and serum antiglomerular basement membrane antibody titer studies confirmed the diagnosis of Goodpasture's syndrome. To our knowledge, this is the first report of renal vein thrombosis as the initial presentation of Goodpasture's syndrome.

Adult↗

Special critical care considerations in tracheostomy management.

The tracheotomized patient undergoing mechanical ventilation presents numerous challenges to the intensive care team. During the initial phase of respiratory failure, patient instability and risks of multiorgan failure focus efforts on an array of critical care management techniques designed to reverse the underlying process and prevent complications. During the stabilization phase, issues of tracheostomy care become equally important in improving patient outcome. These topics include the proper assistance in patient communication, initiation of enteral nutrition, weaning from airway cannulation, and anticipation of adverse reactions after airway decannulation. Failure in promoting a logically conceived and carefully applied treatment plan in any of these areas frequently delays patient recovery and risks serious complications of airway compromise.

Critical Care↗

Timing of tracheotomy in ventilator-dependent patients.

During the last 20 years, improved critical care techniques have enhanced the probability that the condition of patients with respiratory failure will stabilize sufficiently to allow long-term mechanical ventilation. Patients undergoing the transition to prolonged ventilatory support benefit from a timely application of tracheotomy guided by a clear understanding of its risk and benefits. Although numerous investigations since 1970 compare patient outcome from tracheotomy with that after prolonged translaryngeal intubation, limitations of study design and varying results among institutions prevent absolute recommendations for timing tracheotomy. A critical review of the available data, however, allows individualization of care and an anticipatory approach to institution of the surgical airway.

Humans↗

Inhibition of rabbit lung glucose-6-phosphate dehydrogenase by dehydroepiandrosterone augments oxidant injury.

The contribution of lung glucose-6-phosphate dehydrogenase (G-6-PD) activity to pulmonary antioxidant defenses was investigated in the isolated perfused rabbit lung using dehydroepiandrosterone (DHEA), a specific steroidal inhibitor of G-6-PD. Infusion of xanthine oxidase (0.002 U/ml) generated moderate lung edema as measured by increased lung weight and lung lavage albumin content. Infusion of DHEA caused an augmentation of xanthine oxidase-induced lung edema. Hydrostatic factors did not participate in the worsened lung edema because mean pulmonary artery pressures were similar in both experimental groups. Incubation of lung tissue in vitro with DHEA demonstrated ablation of tissue G-6-PD activity without decreasing catalase, glutathione peroxidase, or superoxide dismutase activity. It was concluded that DHEA is a specific inhibitor of lung G-6-PD, and that G-6-PD provides an important antioxidant defense mechanism in preventing oxidant-induced lung injury.

Animals↗

Clinical predictors of prolonged translaryngeal intubation in patients with the adult respiratory distress syndrome.

This study was designed to determine if clinical features apparent after seven days of mechanical ventilation predict long-term intubation beyond 14 days and subsequent need for tracheotomy in patients with ARDS. Twenty-four patients were entered into the study. Group 1 patients were successfully extubated in less than or equal to 14 days after onset of ARDS and group 2 patients remained intubated greater than 14 days. On day 7 of ARDS, group 1 had a higher PaO2/PAO2 ratio, a lower PEEP requirement, less severe chest radiographic abnormalities and a greater likelihood of an improved radiograph from the baseline study. None of group 1 and 11 group 2 patients eventually underwent tracheotomy. Clinical features apparent after seven days of mechanical ventilation in patients with ARDS suggest the likelihood of prolonged intubation beyond 14 days and eventual tracheotomy. Recognition of these features may allow more timely conversion of endotracheal intubation to tracheotomy.

Adult↗