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Biomedical subjects

W R Summer

Publications and source records attributed to W R Summer.

At least 73 records · Page 4Linked to original sources
PubMed1993

Effect of high voltage pulsed galvanic stimulation on sacral transcutaneous oxygen tension levels in the spinal cord injured.

Evidence is mounting that spinal cord injured (SCI) persons may be at increased risk of pressure ulcers due to prolonged immobilization together with the injury-induced loss of sympathetic tone and decreased vascular resistance. With a view to developing a new method of preventing pressure ulcers, the objective of this study was to determine whether high voltage pulsed galvanic stimulation (HVPGS) could increase sacral transcutaneous oxygen tension (PtcO2) in SCI persons lying prone and supine. In experiment 1, HVPGS applied to the back at spinal level T6 led to a sustained, dose-related increase in sacral PtcO2 in 3 subjects lying prone. In experiment 2, carried out on 29 subjects lying supine on egg-crate mattresses, HVPGS (75 volts, 10 Hz) produced a 35% increase in sacral PtcO2, from a baseline level (Mean +/- SD) of 49 +/- 21 mmHg to 66 +/- 18 mmHg after 30 minutes of stimulation (F = 39.4, p < .00001). In experiment 3, simulated HVPGS was found to have no effect on sacral PtcO2 in 5 subjects lying supine. In experiment 4, HVPGS was repeated on 10 subjects and its effects found to be highly reproducible. It is hypothesized that HVPGS restores sympathetic tone and vascular resistance below the level of the spinal cord lesion, thereby increasing the perfusion pressure gradient in the capillary beds. Randomized controlled trials are now indicated to determine the efficacy of HVPGS for preventing pressure ulcers.

Adolescent↗
PubMed1993

Ouabain enhances basal release of nitric oxide from carotid artery.

The authors tested the postulate that ouabain releases nitric oxide (NO) from the vascular endothelium of porcine carotid arteries (PCAs) with the technique of perfusion-superfusion bioassay, in which the perfused PCA with endothelium served as the source of NO and superfused left circumflex coronary artery (CMFX) rings with rubbed endothelium served as the bioassay tissue. Selective exposure of the PCA to ouabain (10 microM) enhanced the basal release of NO but did not affect bradykinin-stimulated (BK; 0.1-100 picomoles) release of NO. The effect of ouabain on basal release of NO from PCA persisted after pretreatment of either PCA or circumflex coronary artery with propranolol (1 microM); ibuprofen (1 microM); and hydrocortisone (10 microM). Finally, selective pretreatment of the PCA with L-NG-monomethylarginine (LNMMA; 100 microM) to inhibit 1-arginine-derived NO synthesis inhibited the relaxation of the circumflex coronary artery to basal, BK, and ouabain-stimulated effluent. Since a nonspecific increase in intracellular calcium ion will enhance both basal and agonist-induced release of NO, the authors conclude that a ouabain-sensitive ATPase is involved in basal release of NO from the endothelium of the PCA. Alternatively, ouabain may act on an isozyme of NO synthase in the vascular endothelium. Speculatively, ouabain-induced stimulation of NO release from vascular endothelium may contribute to the beneficial effect of ouabain in congestive heart failure.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Recombinant cytokines and pulmonary host defense.

The recent discovery of several cytokines and their purification using recombinant DNA technology has uncovered their role as critical factors in pulmonary host defense. The importance of tumor necrosis factor, interferon-gamma, and granulocyte-colony stimulating factor in lung infections was first elucidated in animal models and has been confirmed with neutralization studies. This article reviews these three cytokines, their recent use in human subjects, and their potential use in the future.

Animals↗
PubMed1993

Tumor necrosis factor-alpha inhibits endothelium-dependent relaxation.

Tumor necrosis factor-alpha (TNF-alpha) stimulates nitric oxide (NO) in vascular endothelium by induction of the enzyme NO synthase II (NOS II). We examined the effects of TNF-alpha on 1) endothelium-dependent (EDR) and endothelium-independent (EIR) relaxation and 2) contraction of bovine intralobar pulmonary arteries (BPA) and veins (BPV) in vitro. Acetylcholine (ACh), bradykinin (BK), histamine, and A23187 produced EDR of BPA contracted with a 50% effective concentration of U-46619 (15 nM), because relaxation was abolished by endothelium-rubbing and attenuated by L-NG-mono-methylarginine (L-NMMA; 300 microM). TNF-alpha (0.00417, 0.0417, 0.417, and 1.25 micrograms/ml) incubated with BPA for 60 min inhibited EDR of the BPA to ACh, BK, and histamine. The effects of TNF required 30 min for onset. Recovery of EDR occurred 3-4 h after washout of TNF-alpha. Pentoxifylline (1 microM) did not affect ACh-induced EDR but selectively reversed TNF-alpha-mediated inhibition of ACh-induced EDR. TNF-alpha-mediated inhibition of EDR was not reversible by L-NMMA, an inhibitor of NOS I and NOS II, the cyclooxygenase inhibitor ibuprofen, or CV-3908 (1 microM), a platelet-activating factor antagonist. The inhibitory effect of TNF-alpha on EDR was not mediated by nonspecific sensitization of the endothelium to human protein because recombinant human granulocyte colony-stimulating factor (10, 50, and 500 x 10(3) U/ml) did not affect EDR of BPA. The effect of TNF-alpha was specific for release of NO from the endothelium of BPA because TNF-alpha did not affect 1) EDR of BPV to ACh, BK, or ATP; 2) EIR of BPA or BPV to nitroprusside; and 3) contraction of either BPA or BPV to KCl, U-46619, histamine, norepinephrine, or serotonin. Thus TNF-alpha appears to selectively inhibit receptor-mediated EDR and NO release in BPA. TNF-alpha-mediated inhibition of EDR differs from that of L-arginine-based inhibitors and may represent an endogenous physiological mechanism of regulation of NO in the endothelium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Tumor necrosis factor inhibits stimulated but not basal release of nitric oxide.

Tumor necrosis factor alpha (TNF alpha) increases nitric oxide (NO) synthase in vascular endothelium, but it inhibits endothelium-dependent relaxation (EDR) of vascular smooth muscle. We tested whether TNF alpha inhibits the response to, or release of, NO in bovine pulmonary artery (BPA) using the technique of perfusion-superfusion bioassay and ozone chemiluminescence. Effluent from the perfused BPA with endothelium (donor)-relaxed endothelium-rubbed bovine coronary artery (BCA) (detector). Moreover, effluent from the donor stimulated with acetylcholine (ACh) or bradykinin (BK) (0.001 to 100 nmol) relaxed the detector. Direct application of these agonists to the detector failed to produce relaxation. Basal and agonist-stimulated effluent from the donor treated with L-NG-monomethylarginine (LNMMA) (100 microM) suppressed effluent-mediated relaxation of the detector. ACh and BK released LNMMA-inhibitable nitrite and nitrate from the BPA. Thus, the effluent contained NO. Exposure of the donor to TNF alpha (1.25 micrograms/ml) for 60 min did not affect basal release of NO, but it attenuated bioassayable and chemiluminescence-detectable NO release by ACh and BK. The inhibition of NO release was directly related to the magnitude of inhibition of EDR by ACh and BK. Thus, TNF alpha selectively inhibits receptor-mediated release of NO without affecting basal release of NO. This effect differs from that of L-arginine-based inhibitors of NO and represents a unique physiologic mechanism of regulation of NO in the endothelium.

Acetylcholine↗
PubMed1993

Alveolar macrophage release of tumor necrosis factor during murine Pneumocystis carinii pneumonia.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine produced principally by mononuclear cells, is released in response to a variety of pulmonary pathogens. We hypothesized that release of TNF in the lung is a normal part of the host response to intratracheal challenge with Pneumocystis carinii. To test this hypothesis, we measured TNF in bronchoalveolar lavage fluid (BALF) in normal and CD4-depleted mice at various intervals in acute and chronically infected animals. To assess the cell of origin and the control of TNF release in the lung, we measured mRNA for TNF by a competitive polymerase chain reaction and assessed the capacity of adherence-enriched cells to produce TNF in vitro in response to lipopolysaccharide. Our data demonstrate that TNF peaks at 3 h in both control and CD4-depleted mice after acute challenge with P. carinii and this increase in TNF precedes the influx of inflammatory cells into the lung. TNF levels in BALF return to undetectable levels by day 3. In chronically infected animals, there is a 5-fold increase in mRNA for TNF in adherent cells which is associated with an increased capacity to release TNF in vitro. These data suggest that TNF is a normal host response to P. carinii infection; however, there is no difference in acute TNF release between control animals that clear their infection and CD4-depleted animals that develop chronic infection. TNF is upregulated in chronically infected animals, but CD4 depletion results in the loss of additional host factors essential for resolution of this infection.

Animals↗
PubMed1993

Effect of air-supported, continuous, postural oscillation on the risk of early ICU pneumonia in nontraumatic critical illness.

STUDY OBJECTIVES: We hypothesized that continuous, automatic turning utilizing a patient-friendly, low air loss surface would reduce the incidence of early ICU pneumonia in selected groups of critically ill medical patients. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Medical ICU of a large community teaching hospital. PATIENTS: One hundred twenty-four critically ill new admissions to the medical ICU at Charity Hospital in New Orleans. INTERVENTIONS: Patients were prospectively randomized within one of five diagnosis-related groups (DRG)--sepsis (SEPSIS), obstructive airways disease (OAD), metabolic coma, drug overdose, and stroke--to either routine turning on a standard ICU bed or to continuous turning on an oscillating air-flotation bed for a total of five days. MEASUREMENTS AND RESULTS: Patients were monitored daily during the treatment period for the development of pneumonia. The incidence of pneumonia during the first five ICU days was 22 percent in patients randomized to the standard ICU bed vs 9 percent for the oscillating bed (p = 0.05). This treatment effect was greatest in the SEPSIS DRG (23 percent vs 3 percent, p = 0.04). Continuous automatic oscillation did not significantly change the number of days of required mechanical ventilation, ICU stay, hospital stay, or hospital mortality overall or within any of the DRGs. CONCLUSIONS: We conclude that air-supported automated turning during the first five ICU days reduces the incidence of early ICU pneumonia in selected DRGs; however, this form of automated turning does not reduce other measured clinical outcome parameters.

Beds↗
PubMed1992

Effect of dichloroacetate on mechanical performance and metabolism of compromised diaphragm muscle.

We investigated the effect of dichloroacetate (DCA) on tension generation and carbohydrate metabolism of the rat diaphragm in vitro. Isolated diaphragms were placed in individual organ chambers and were hooked to force-displacement transducers. Net lactate production and glucose and lactate oxidation were measured in vitro. Diaphragmatic fatigue was precipitated by in vivo endotoxemic shock, by in vitro hypoxia, or by in vitro repetitive tetanic stimulation. In diaphragms isolated from endotoxemic rats, DCA increased tension generation by 30 and 20% at stimulation frequencies of 20 and 100 Hz, respectively. Associated with changes in mechanical performance, DCA reduced net lactate production by 53% after 60 min of incubation and increased glucose oxidation 54% but had no effect on lactate oxidation. During in vitro hypoxia, DCA reduced net diaphragmatic lactate production by 30% and increased glucose oxidation by 45% but did not attenuate hypoxic fatigue. DCA had no effect on tension generation during repetitive tetanic stimulation. We conclude that DCA improves in vitro diaphragmatic fatigue due to endotoxicosis but not due to hypoxia or repetitive stimulation.

Animals↗
PubMed1991

Myocardial metabolic effects of in vivo hydralazine treatment of streptozotocin-diabetic rats.

We determined myocardial pumping capacity, glucose oxidation, and mechanical response to ischemia in streptozotocin-diabetic rats treated for 4 wk with or without hydralazine (0.5 mg/g of chow). Plasma triglycerides and cholesterol were decreased 73 and 50%, respectively, in the treated animals. Blood glucose levels were greater than 400 mg/100 g in both groups. Hearts were perfused in the working configuration with buffer containing 5 mM [U-14C]glucose. Starling curves were constructed by increasing left atrial filling pressure from 5 to 20 cm of water. Diabetic heart mechanical function was depressed compared with control and hydralazine treatment restored function to normal. Oxidation of [U-14C]glucose was comparably depressed in the treated and untreated diabetics. The provision of 1 mM dichloroacetate in the perfusate increased glucose oxidation in the hearts from hydralazine-treated rats, however. Twenty minutes of global ischemia resulted in 65% decrease in mechanical function in the hearts of hydralazine-treated group vs. 15% for hearts from nontreated diabetics. The data suggest that measures to normalize lipid metabolism may not normalize myocardial glucose oxidation or permit better mechanical recovery after ischemia in the diabetic myocardium.

Animals↗
PubMed1991

Analysis of responses to endothelins in the rabbit pulmonary and systemic vascular beds.

The effects of two isoforms of human endothelin (ET) on the pulmonary and systemic vascular beds were compared in the anesthetized intact-chest rabbit under conditions of constant pulmonary blood flow and left atrial pressure. Intralobar bolus injections of ET-1 (0.1-1 micrograms) and ET-3 (1-3 micrograms) produced modest vasoconstriction in the pulmonary vascular bed, whereas both peptides decreased systemic arterial pressure. The pulmonary vasoconstrictor response to ET-1 and ET-3 was inhibited by intralobar infusion of nitrendipine but was not altered by indomethacin. In contrast to the small effects of ET-1 and ET-3 on intact pulmonary resistance vessels, both peptides markedly contracted isolated pulmonary conductance vessels, with greater activity on venous than on arterial segments. Intravenous bolus injection of ET-1 (0.1-0.3 micrograms) or ET-3 (0.3-1 microgram) decreased systemic arterial pressure, increased cardiac output, and markedly decreased systemic vascular resistance. Higher doses of ET-1 produce a biphasic systemic vascular response with a prominent secondary pressor component. The present data suggest that the pulmonary vasoconstrictor activity of ET-1 is greater than that of ET-3 and their pressor activity depends on an extracellular source of calcium. The pulmonary and systemic hemodynamic effects of ET-1 and ET-3 in the rabbit do not depend on cyclooxygenase products. The systemic vasodilator response to ET-1 is not altered by first-pass lung transit. Furthermore the systemic vasodilator response to both peptides occurs independent of activation of muscarinic, beta 2-adrenergic, and platelet-activating factor receptors. Although ET-1 and ET-3 were initially reported as vasoconstrictor peptides, the present data suggest that, by having unique and potent systemic vasodilator activity, ET-1 and ET-3 act differently in the systemic and pulmonary vascular beds under resting conditions in the rabbit.

Animals↗
PubMed1990

Endotoxin-induced suppression of lung host defenses.

Respiratory tract infections are major causes of excessive morbidity and mortality in hospitalized patients. Persons with systemic sepsis have an especially high risk of acquiring these infections, which indicates that their lung antibacterial defenses are compromised. To evaluate the effects of sepsis on pulmonary antibacterial defenses, we injected either saline or 5 mg/kg of Escherichia coli lipopolysaccharide intravenously into Sprague-Dawley rats. Two hours later, the animals were challenged by aerosol inhalation with either Staphylococcus aureus or Pseudomonas aeruginosa. It is known that phagocytic defenses against aerosolized S. aureus challenges are provided solely by the alveolar macrophage; in normal animals challenged with P. aeruginosa, however, an intrapulmonary inflammatory response is elicited. Animals pretreated with endotoxin showed a significant decrease in pulmonary bactericidal activity against S. aureus with 31 +/- 3% bacteria remaining viable at 4 hr compared with 20 +/- 2% in the controls, which indicates a defect in alveolar macrophage antimicrobial activity. After P. aeruginosa challenge, saline-injected control animals developed a marked intrapulmonary inflammatory response and killed greater than 85% of their initial inoculum by 4 hr. By contrast, endotoxin-treated animals failed to recruit neutrophils into the alveoli in response to P. aeruginosa, resulting in a proliferation of this pathogen within the lung (212 +/- 6% bacteria remaining viable at 4 hr). Endotoxin is known to be a potent stimulus for the production of tumor necrosis factor (TNF) by the host. TNF is a potent inflammatory mediator and promotes neutrophil adhesion to the vascular endothelium. In these experiments, serum TNF peaked at 28,390 +/- 7,766 Units/ml. 90 min after intravenous endotoxin. Histopathology of the lungs in these animals showed considerable sequestration of the neutrophils within the pulmonary vasculature. These data show that systemic endotoxin significantly impairs lung host defenses against intrapulmonary bacterial challenges and suggest that TNF-mediated events may play a central role.

Animals↗
PubMed1989

Alveolar cell carcinoma complicating sickle cell anemia: a chance occurrence?

Alveolar cell carcinoma, a neoplasm associated with pre-existing inflammatory lung disease, has not been reported previously in patients with sickle cell disease. We present such a patient and suggest that chronic pulmonary scarring in this setting predisposed to development of his malignancy. As survival increases in individuals with sickle cell disease, alveolar cell carcinoma must be considered in these differential diagnosis of otherwise unexplained chronic pulmonary infiltrates.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1989

The effect of dichloroacetate on the isolated no flow arrested rat heart.

Ischemic dysfunction, including contracture, has been attributed to lack of ATP, although previous work has not been consistent with this concept. We describe here a model of no flow ischemic arrest, characterized by depressed levels of mechanical function upon reperfusion and high energy phosphate stores within normal limits. The decreased mechanical function bears an inverse relationship to myocardial lactate levels after twenty-minutes of reperfusion in the absence or presence of dichloroacetic acid (DCA). Post-ischemic non-DCA treated hearts attained peak work of only 25% of that of controls, while those treated with DCA following ischemia performed almost as well as controls. ATP and CP levels remained high in both DCA treated and non-DCA treated hearts. Lactate levels were high in hearts immediately following ischemia, but were reduced to control levels in post-ischemic hearts perfused with DCA within twenty minutes, whereas those not treated with DCA had lactate levels two to three times that of controls within the same time period. Pyruvate dehydrogenase (PDH) activity was reduced in non-DCA treated post ischemic hearts after twenty minutes reperfusion but was elevated above controls in hearts reperfused with DCA. The data indicates that DCA increases mechanical performance of the isolated post-ischemic rat heart and the proposed mechanism for this increase is the oxidative removal of lactate resulting from an increase in PDH activity.

Acetates↗
PubMed1989

Endothelin--a new family of endothelium-derived peptides with widespread biological properties.

Endothelin (ET) is a novel family of three isopeptides (ET-1, ET-2, ET-3) each containing twenty-one amino acids and two disulfide bonds. Initially isolated from the supernatant of cultured porcine aortic endothelial cells, ET is stored as a preproform and released through an unusual proteolytic cleavage. In general, ET-1, ET-2, ET-3 differ quantitatively but not qualitatively in their biologic activity. ET have potent contractile activity in a variety of isolated tissues including arteries veins, trachea, duodenum urinary bladder and uterus. In vivo, ET possesses potent vasodilator and vasoconstrictor properties. Although the mechanisms mediating the hemodynamic effects of ET are not entirely clarified, recent evidence indicates a role for endothelium-derived relaxant factor (EDRF), protein kinase C and extracellular calcium. Moreover, ET appears to produce inflammation and bronchoconstriction through the formation of arachidonic acid metabolites via the cyclooxygenase pathway. The presence of ET binding sites in blood vessels and in several organ systems suggests ET may have important regulatory functions, which remain to be determined.

Amino Acid Sequence↗
PubMed1989

Alcohol suppresses lipopolysaccharide-induced tumor necrosis factor activity in serum and lung.

Ethanol intoxication has been shown to suppress selected functions of the immune system thereby compromising host defense against bacterial infections. Tumor necrosis factor, a secretory protein produced by the macrophage in response to lipopolysaccharide, mediates the inflammatory cascade and stimulates phagocyte functions. Acute ethanol intoxication markedly suppressed both serum and lung tumor necrosis factor elicited in response to lipopolysaccharide. Furthermore, ethanol inhibited intratracheal lipopolysaccharide-induced neutrophil recruitment into the alveoli and prevented the fall in circulating neutrophils in response to intravenous lipopolysaccharide. Thus, the anti-inflammatory effects of ethanol may be secondary to suppression of macrophage-derived tumor necrosis factor.

Animals↗
PubMed1989

A comparison of interposed abdominal compression CPR and standard CPR by monitoring end-tidal PCO2.

Interposed abdominal compression CPR (IAC-CPR) has been demonstrated to significantly improve blood flow compared with standard (S)-CPR in animal and electrical models. Studies with IAC-CPR in human beings have not reported data regarding cardiac output. Animal and clinical studies have correlated end-tidal PCO2 (ETPCO2) with cardiac output produced with precordial compressions. We conducted a prospective, randomized study on 33 adult patients with nontraumatic cardiac arrest. Patients were randomized to initially receive either S-CPR or IAC-CPR. ETPCO2 was monitored continuously. After 20 minutes of resuscitation, the technique was reversed. The average ETPCO2 during IAC-CPR was 17.1 mm Hg while the average during S-CPR was 9.6 mm Hg, a difference of 78% (P less than .001). In patients arriving in cardiac arrest, return of spontaneous circulation was observed in six patients (30%) during IAC-CPR and in one patient (6%) during S-CPR (P = .07). Our study strongly suggests that cardiac output may be significantly increased in human beings with IAC-CPR as evidenced by the significantly greater increases in ETPCO2 with IAC-CPR compared with S-CPR. In addition, IAC-CPR appeared to demonstrate a trend toward increasing the return of spontaneous circulation.

Abdomen↗