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Biomedical subjects

J E Grossman

Publications and source records attributed to J E Grossman.

At least 19 recordsLinked to original sources

Regulation of leukocyte function by nitric oxide donors: the effect of S-nitroso-thiol complexes.

The aim of this study was to evaluate the effectiveness of a novel protein-bound S-nitroso-thiol, S-nitroso-albumin (S-NO-alb), in modulating neutrophil-endothelial cell adhesion, activation, and interactions. Due to the highly variable kinetics of NO release from the low-molecular-weight thiol adducts S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-glutathione (GSNO), we expected S-NO-alb to be a more effective modulator of inflammatory interactions through its slow, steady, and prolonged release of NO. Human umbilical-vein endothelial cells (HUVECs) challenged with lipopolysaccharide (LPS) demonstrated upregulated adhesion of neutrophils that was significantly attenuated by pretreatment with S-NO-alb (1.0-100 microM) (p < .05), but not SNAP or GSNO. Pretreatment with S-NO-alb, SNAP, or GSNO attenuated tumor necrosis factor-alpha primed *O2- release from neutrophils and increased neutrophil cGMP accumulation. On a molar basis, S-NO-alb expressed a 10-fold greater potency than SNAP or GSNO at modulating these effects. Kinetics studies confirmed the relative stability of spontaneous NO release from S-NO-alb compared with highly variable kinetic profiles of SNAP and GSNO. Our results demonstrate that S-NO-alb more effectively modulates endothelial-cell and neutrophil immunoinflammatory responses versus its related low-molecular-weight thiol complexes.

Cell Adhesion↗

Low molecular weight heparin alters porcine neutrophil responses to platelet-activating factor.

Because platelet-activating factor (PAF) is an important mediator of inflammation and heparin has anti-inflammatory effects, we hypothesized that low molecular weight heparin (LMWH) would inhibit PAF-induced activation and chemotaxis in porcine neutrophils. Citrated blood was obtained from pentobarbital-anesthetized pigs, and neutrophils were isolated over a 55%/65% Percoll gradient. The effect of LMWH on basal phorbol myristate acetate (PMA)-induced superoxide (SO) release, as well as its effect on PAF priming for PMA-induced SO release, were investigated. Additionally, the effect of LMWH on PAF-induced chemotaxis of neutrophils across transwell membranes was evaluated. Baseline SO release in response to PMA was .351+/-.046 nmol/10(6) cells/min, and this was decreased to .289+/-.034 nmol/10(6) cells/min by pretreatment with 50 U/mL LMWH. PMA-induced SO production was increased by .240+/-.042 nmol/10(6) cells/min when cells were primed with 10 microM PAF. This priming effect of PAF was reduced significantly by pretreatment of neutrophils with LMWH at 10 and 50 U/mL. Chemotaxis of neutrophils in response to 100 microM PAF was significantly decreased to 70.02+/-6.4% (n = 8) of the control response by pretreatment of cells with 50 U/mL LMWH. We conclude that LMWH has anti-inflammatory effects on porcine neutrophils, which includes attenuation of cell activation and chemotaxis in response to the lipid-derived inflammatory mediator, PAF.

Animals↗

E-mail access to NetCME: implementation of server push paradigm.

We describe the implementation of a Continuing Medical Education project which utilizes e-mail delivery of HTML documents to facilitate participant access to case material. HTML e-mail is displayed directly within the e-mail reader of the Netscape browser. This system of proactive educational content delivery ensures simultaneous distribution to all participants. Although a more effective method of content distribution, the system preserves user confidentiality and maintains security. HTML e-mail is non-proprietary and could be integrated into existing Internet-based educational projects to facilitate user access.

Computer Communication Networks↗

Attenuation of endotoxin-induced pathophysiology by a new potent PAF receptor antagonist.

The role of platelet-activating factor (PAF) as a mediator of endotoxin-induced pathophysiology has been studied in several animal models with conflicting results. We evaluated the effect of a new, potent, and specific PAF receptor antagonist, ABT-299 (Abbott Laboratories) against endotoxin (lipopolysaccharide; LPS)-induced cardiopulmonary dysfunction in a porcine model. In initial experiments, the potency of ABT-299 was confirmed in vitro by its ability to inhibit PAF-induced porcine platelet aggregation at an IC50 of .047 +/- .01 microM, and in vivo by the ability of low doses (.12 mg/kg + .03 mg/kg/h) to block the cardiopulmonary pathologic response to exogenous PAF infusion. To evaluate the effect of ABT-299 administration during endotoxemia, pigs were randomly assigned to one of three groups: controls (n = 7), LPS (n = 9), or ABT-299 + LPS (n =7). ABT-299 was given at 1.0 mg/kg from -0.5 to 0 h plus .3 mg/kg/h from 0 to 6 h. LPS was given at .5 micrograms/kg/hr from 0 to 6 h. ABT-299 reduced the early LPS-induced fall in cardiac index and stroke volume, pulmonary hypertension and vasoconstriction, bronchoconstriction, and hypoxemia. Administration of LPS resulted in 44% mortality (before 6 h), which was blocked by ABT-299. Results with this antagonist indicate that PAF contributes to endotoxin-induced cardiopulmonary dysfunction in the pig, and is associated with mortality in this model.

Animals↗

Treatment of refractory sleep apnea with supplemental carbon dioxide.

Sleep apnea syndrome is a relatively common disorder characterized by periodic cessation of breathing during sleep because of upper airway obstruction (obstructive sleep apnea) or by reduction of ventilatory drive (central sleep apnea). We report the case of a middle-aged, obese man who underwent tracheostomy for the treatment of obstructive sleep apnea documented by polysomnography. Although tracheostomy resulted in marked clinical improvement, relief of upper airway obstruction unmasked severe central sleep apnea. We report the successful treatment of this patient's central sleep apnea syndrome with the use of supplemental CO2 therapy.

Adult↗

Acute myopathy during treatment of status asthmaticus with corticosteroids and steroidal muscle relaxants.

Acute myopathy in patients being treated for severe asthma has been recognized with increasing frequency since first being described in 1977. We report three patients treated for status asthmaticus who developed severe generalized weakness. Electrophysiologic studies and muscle biopsy revealed evidence of muscle destruction. Each of these patients was treated with high-dose corticosteroids and underwent prolonged neuromuscular blockade with a steroidal muscle relaxant. A review of the literature revealed 15 similar cases. We postulate that the combined effects of corticosteroids and muscle relaxants on the muscle cell may be responsible for this myopathy. Patients treated with corticosteroids and NMBs should be carefully monitored for the development of myopathy.

Acute Disease↗

Differential effects of eicosapentaenoic acid and oleic acid on lipid synthesis and secretion by HepG2 cells.

The effects of eicosapentaenoic acid and oleic acid on lipid synthesis and secretion by HepG2 cells were examined to identify fatty acid specific changes in lipid metabolism that might indicate a basis for the hypolipidemic effect attributed to eicosapentaenoic acid and related n-3 fatty acids. Cellular glycerolipid synthesis, as determined by [3H]glycerol incorporation, increased in a concentration-dependent manner in cells incubated 4 h with either eicosapentaenoic acid or oleic acid at concentrations between 10 and 300 microM. [3H]Glycerol-labeled triglyceride was the principal lipid formed and increased approximately fourfold with the addition of 300 microM oleic acid or eicosapentaenoic acid. Both fatty acids also produced a 20-40% increase in the total cellular triglyceride mass. Although both fatty acids increased triglyceride synthesis to similar extents, eicosapentaenoic acid-treated cells secreted 40% less [3H]glycerol-labeled triglyceride than cells fed oleic acid. Cellular synthesis of [3H]glycerol-labeled phosphatidylethanolamine and phosphatidylcholine was also reduced by 40% and 30%, respectively, in cells given eicosapentaenoic acid versus cells given oleic acid. Similar results were obtained in determinations of radiolabeled oleic acid and eicosapentaenoic acid incorporation. At a fatty acid concentration of 300 microM, incorporation of radiolabeled eicosapentaenoic acid into cellular triglycerides was greater than the incorporation obtained with radiolabeled oleic acid, while the reverse relationship was observed for the formation of phosphatidylcholine from the same fatty acids. Eicosapentaenoic acid is as potent as oleic acid in inducing triglyceride synthesis but eicosapentaenoic acid is a poorer substrate than oleic acid for phospholipid synthesis. The intracellular rise in de novo-synthesized triglyceride in eicosapentaenoic acid-treated cells without corresponding increases in triglyceride secretion suggests that eicosapentaenoic acid is less effective than oleic acid in promoting the transfer of de novo-synthesized triglyceride to nascent very low density lipoproteins.

Chromatography, High Pressure Liquid↗

Sphenoid fractures: prevalence, sites, and significance.

The computed tomographic (CT) scans of the head of 490 blunt trauma victims were reviewed to establish the frequency of sphenoid fractures. There were 111 patients with craniofacial fractures, 78 of whom had fractures of the sphenoid bone. In 51 of the 78 patients these were associated with complex facial fractures, and in the 27 remaining patients they represented primarily fractures of the skull base. The number of sphenoid fractures not only exceeded those that involved the other bones of the base of the skull, including the temporal bone, but also exceeded the number of fractures of the cranial vault that could be identified with CT. All available charts were reviewed for the patients with sphenoid fractures in order to determine the presence of potentially related injuries. In 21 patients there were complications that included damage to the internal carotid artery, cerebrospinal fluid rhinorrhea, optic nerve damage, superior orbital fissure syndrome, and posttraumatic diabetes insipidus.

Accidents, Traffic↗

Positional changes in gas exchange after unilateral pulmonary embolism.

We describe positional changes in oxygenation in two patients with respiratory failure due to massive pulmonary embolism. In both patients, oxygenation improved when the "sick" lung was dependent and deteriorated when the "healthy" lung was in the dependent position. These positional changes are different from previously reported changes in unilateral pulmonary disease. We speculate that a combination of unilateral pulmonary embolism and mechanical ventilation was responsible for the improvement in gas exchange when the "sick" lung was placed in the dependent position. The relative contribution of these two components to the development of this phenomenon is unclear.

Aged↗

Effect of naproxen, a prostaglandin inhibitor, on acute otitis media and persistence of middle ear effusion in children.

Prostaglandins are thought to be of importance in the pathophysiology of otitis media with effusion (OME), and the possibility of reducing the frequency and persistence of this condition by using prostaglandin inhibitors has been suggested. In a double blind manner, naproxen was administered to children with acute otitis media, in addition to amoxicillin, and its influence on the subsequent occurrence and persistence of middle ear effusion was evaluated. Eighty-one children participated in the study. No significant difference was found in the number of patients with tympanograms consistent with OME in the two groups. After 10 days of treatment, 63% in the naproxen and 58% in the placebo group, and after 30 days, 41% and 59%, respectively, had type B tympanograms. Similarly, there were no differences between the two groups with respect to other parameters studied (duration of otalgia, fever, otoscopic findings). No side effects related to naproxen were observed.

Acute Disease↗

Tears of the trachea and main bronchi caused by blunt trauma: radiologic findings.

Although most of the radiologic changes that have been described in transection or laceration of the trachea or main bronchi are nonspecific, they can be of diagnostic importance in the appropriate clinical setting. In order to reassess the significance of these findings, and to determine the presence of any other changes that might lead to a definitive diagnosis, we retrospectively reviewed the chest radiographs of nine patients who had tears or transection of the trachea and/or main bronchi as a result of blunt chest trauma. The diagnosis was proved by bronchoscopy in all patients and reconfirmed at surgery in five. The predominant findings on the chest radiographs were related to air leak and included subcutaneous emphysema (seven patients), pneumomediastinum (seven patients), pneumothorax (six patients), and air surrounding a bronchus in one patient. Upper thoracic fractures that involved the clavicles, scapula, sternum, and ribs were present in four patients. Abnormalities in the appearance of an endotracheal tube in two patients (overdistention of the cuff or extraluminal position of the tip), and the presence of the fallen lung sign (collapse of the lung toward the lateral chest wall) in two others provided specific evidence of tracheobronchial injury. We conclude that, although the major importance of the chest radiograph in patients with tracheobronchial transection may be to verify the existence of air leak, the presence of the fallen lung sign and endotracheal tube abnormalities is a reliable indication of airway injury.

Adolescent↗

An immunocytochemical method for quantification of lung tissue fibronectin.

A technique to quantify tissue fibronectin was developed, using peroxidase-antiperoxidase immunocytochemistry and automated scanning light microscopy. This technique was developed using isolated perfused rat lungs, some of which were subjected to acute oxidant lung injury. Both injured and control lungs were perfused with solutions containing heterologous fibronectin. The technique clearly demonstrated differences in the amount of tissue fibronectin in injured and noninjured lung as well as differences between lungs exposed to fibronectin and those not exposed. The described technique offers a reliable method for quantifying tissue fibronectin and is sensitive enough to detect differences in tissue fibronectin under experimental conditions of acute lung injury.

Animals↗

Risk factors of anesthesia and surgery in bleomycin-treated patients.

The use of bleomycin as part of preoperative chemotherapy regimens for nonseminomatous germ cell tumors of the testis has gained increased acceptance. However, recent experience has suggested that patients so treated are at an increased risk of developing postoperative respiratory distress syndrome. The most clearly associated factor seems to be the fractional concentration of inspired oxygen intraoperatively and in the immediate postoperative period. Based on our experience and a review of the limited published reports, we recommend careful monitoring of fractional inspired oxygen and maintenance of the lowest tolerated oxygen concentration during this period.

Adult↗

Response of plasma fibronectin to major body burn.

The ability of macrophages of phagocytize particulate matter is largely dependent on fibronectin, a nonspecific opsonin found in plasma. Fibronectin depletion, resulting in reticuloendothelial system (RES) depression, occurs following a variety of physical insults. RES depression may contribute to postinjury sequelae such as respiratory distress syndrome and septicemia. Fibronectin concentration was measured in the plasma of sheep with chronic lung lymph fistulas subjected to controlled thermal injury. Fibronectin levels were significantly (p < 0.05) decreased at 4, 24, 48, and 72 hours following burning. Fibronectin concentration decreased in parallel with serum albumin concentration; serum globulin concentrations did not decrease. Fibronectin concentration had an inverse relationship to lung lymph flow, a reflection of pulmonary transvascular fluid filtration rate. The role of fibronectin in the pathogenesis of postinjury respiratory distress syndrome deserves further exploration.

Adult↗