Biomedical subjects

S R White

Publications and source records attributed to S R White.

At least 73 records · Page 4Linked to original sources

PubMed1993

Prostaglandin secretion by guinea pig tracheal epithelial cells caused by eosinophil major basic protein.

We examined the effect of eosinophil major basic protein (MBP) on prostaglandin (PG) secretion from guinea pig tracheal epithelial (GPTE) cells. Primary cultures of GPTE cells were incubated with 10(-6) M MBP for up to 6 h and then stimulated with 10(-6) M bradykinin (BK). PGE2, 6-ketoprostaglandin F1 alpha (PGF1 alpha), PGF2 alpha, and thromboxane B2 (TxB2) concentrations in media were determined by enzyme-linked immunoabsorbent assay (EIA). Incubation with MBP for 6 h caused secretion of both PGE2 (17,614 +/- 4,416 vs. 1,426 +/- 555 pg/10(6) cells at baseline, P < 0.001, n = 7) and PGF2 alpha (20,303 +/- 5,724 vs. 3,790 +/- 1.075 pg/10(6) cells at baseline, P < 0.002, n = 7). Secretion of PGE2 and PGF2 alpha stimulated by MBP required at least 2 h. Incubation with MBP for 6 h also augmented the subsequent response to BK: PGE2 secretion was 29,215 +/- 6,853 vs. 3,445 +/- 1,041 pg/10(6) cells for BK alone (P < 0.0001), and PGF2 alpha secretion was 25,407 +/- 6,237 vs. 5,213 +/- 1,535 pg/10(6) cells for BK alone (P < 0.0001). MBP did not change 6-keto-PGF1 alpha and TxB2 secretion. Incubation of GPTE cells from seven animals with polylysine, a protein with mass and ion charge similar to MBP, for 2 h, both caused secretion of PGE2 (8,579 +/- 3,244 vs. 788 +/- 419 pg/10(6) cells at baseline, P < 0.01) and augmented the response to BK (12,732 +/- 4,788 vs. 1,653 +/- 680 pg/10(6) cells after BK alone, P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of activated eosinophils cultured from human umbilical cord blood on guinea pig trachealis.

We studied the biochemical indexes and corresponding induction of airway smooth muscle contraction and hyperresponsiveness in guinea pig trachealis in situ caused by cultured eosinophils derived from mononuclear cell fractions of human umbilical cord blood. A method was developed that permitted isolation of large numbers of cells (approximately 2.6 x 10(6)/ml cord blood) having morphological and immunohistological characteristics of human peripheral blood eosinophils. After activation with 10(-6) M formyl-Met-Leu-Phe + 5 micrograms/ml cytochalasin B (fMLP + B), in situ application to the epithelial surface of 6 x 10(6) cord-derived eosinophils (CDE)/surface area (cm2) caused 1.46 +/- 0.24 g/cm maximal active tracheal tension in guinea pig tracheal smooth muscle (P < 0.005 vs. zero baseline). Muscarinic responsiveness also was augmented in situ in trachealis preparations treated with activated 3-wk CDE. Contraction caused by 3 x 10(-7) mol/kg iv methacholine (MCh) was 0.94 +/- 0.18 g/cm at baseline vs. 1.80 +/- 0.24 g/cm after activated CDE (P = 0.02). Control (sham-activated) 3-wk CDE caused neither significant contraction [0.41 +/- 0.16 g/cm active tension (AT); P < 0.05 vs. fMLP+B] nor augmented muscarinic responsiveness. Cells cultured for 5 wk contained fewer granules than 3-wk CDE and also caused less direct contraction of trachealis (0.73 +/- 0.14 g/cm AT) after activation (P < 0.01 vs. 3-wk CDE). Both contraction and muscarinic augmentation were blocked in 3-wk CDE after blockade of leukotriene C4 (LTC4) synthesis by pretreatment with the 5-lipoxygenase inhibitor, A63162 (50 microM). Treatment with A63162 had no effect on the stimulated release of eosinophil peroxidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Physiologic significance of epithelial removal on guinea pig tracheal smooth muscle response to acetylcholine and serotonin.

We studied the modulatory effect of airway epithelium on guinea pig tracheal smooth muscle (TSM) contraction. Isometric force was measured in vivo before and after removal of the tracheal epithelium. In parallel studies, TSM contraction was also measured isometrically in epithelium-intact and epithelium-denuded TSM strips in vitro. Epithelial removal in vivo did not alter the contractile response of TSM to acetylcholine (ACh) or serotonin. In nine guinea pigs, active tension (AT) caused by 3 x 10(-7) mol/kg of intravenous ACh was 0.74 +/- 0.14 g force per longitudinal length of the segment (g/cm) in the presence of epithelium versus 0.89 +/- 0.16 g/cm after removal of airway epithelium (confirmed histologically) (p NS). The threshold response to ACh was also unchanged (-8.0 +/- 0.3 log mol/kg control versus -8.3 +/- 0.3 log mol/kg after epithelial removal, p NS). In six guinea pigs, the AT caused by 3 x 10(-8) mol/kg of intravenous serotonin was 1.92 +/- 0.63 g/cm with an intact epithelium versus 2.15 +/- 0.70 g/cm after epithelial removal in vivo (p NS). Epithelial removal in vitro increased the sensitivity of TSM contraction to ACh when the data were expressed as the percentage maximal response to ACh. The concentration of ACh causing 50% of the maximal response (EC50) was -5.74 +/- 0.25 log M in eight epithelium-intact TSM strips versus -6.37 +/- 0.16 log M after epithelial removal in controls (n = 8) (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

Proliferation of guinea pig tracheal epithelial cells induced by calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP) is contained within and secreted by nerves and neuroepithelial bodies in the airway epithelium. To determine whether CGRP is mitogenic for airway epithelial cells, tracheal epithelial cells isolated from 26 guinea pigs were grown in primary culture for 2 days. Subconfluent cells were exposed to 10(-13) to 10(-9) M CGRP for 4 h and then returned to CGRP-free medium. Proliferation was quantified by direct cell count and by measurement of fractional labeling with the thymidine analog, bromodeoxyuridine (BrdU). CGRP exposure increased both cell number (53,980 +/- 9,870 cells after 10(-9) M CGRP versus 33,910 +/- 5,150 cells after control, P < 0.05) and fractional BrdU labeling (12.9 +/- 2.2% after 10(-11) M CGRP versus 3.9 +/- 0.9%, control; P < 0.01, n = 9) at 24 h after exposure. The mitogenic effect of CGRP persisted at least 3 days after exposure. CGRP-induced proliferation was attenuated by co-incubation with the CGRP receptor antagonist, hCGRP-(8-37). These data demonstrate that CGRP causes proliferation of guinea pig tracheal epithelial cells in primary culture through stimulation of a specific receptor, and suggest a role for this neuropeptide in regulating airway epithelial cell growth.

Animals↗

PubMed1993

Selective regulation of expression of surface adhesion molecules Mac-1, L-selectin, and VLA-4 on human eosinophils and neutrophils.

We studied the differential expression of cellular adhesion molecules on the surface of purified human eosinophils and neutrophils caused by ex vivo activation with platelet-activating factor (PAF), formylmethionylleucylphenylalanine (FMLP), or recombinant human interleukin-5 (IL-5). PAF (10(-7) M) caused a 42.8 +/- 5.7% (mean +/- SEM) increase in Mac-1 expression in eosinophils (P < 0.01) and a 34.6 +/- 9.2% increase in Mac-1 expression in neutrophils (P < 0.05). PAF also caused a decrease in L-selectin expression in eosinophils (-37.0 +/- 8.1%, P < 0.001) and neutrophils (-14.1 +/- 3.2%, P < 0.05). FMLP (10(-6) M) caused a similar increase in Mac-1 expression in both eosinophils (P < 0.001 versus controls) and neutrophils (P < 0.01) and a comparable decrease in L-selectin expression in both eosinophils and neutrophils (P < 0.01). In contrast to the effects of PAF and FMLP, IL-5 affected selectively the surface expression of adhesion molecules in eosinophils but not neutrophils. Expression of Mac-1 increased by 44.3 +/- 7.5% in eosinophils (P < 0.001 versus controls) and by 0.7 +/- 1.2% in neutrophils (P = NS versus controls) after exposure to 10(-9) M IL-5. IL-5 also caused a 49.5 +/- 4.2% decrease in eosinophil L-selectin expression (P < 0.001) but had no effect on L-selectin expression in neutrophils. Eosinophil VLA-4 expression was not altered by any stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗

PubMed1993

Regulation of human eosinophil degranulation and activation by endogenous phospholipase A2.

The unique granular proteins of eosinophils may have a pathogenetic role in asthma and in the defense against parasitic infestations. However, the mechanisms regulating eosinophil degranulation are largely unknown. We examined the hypothesis that release of these proteins is regulated by endogenous activation of phospholipase A2. Human eosinophils (HE) were isolated from the peripheral blood of 42 subjects either by Percoll density separation or by negative-selection immunomagnetic fractionation. Eosinophil activation was initiated in vitro with 10(-6) M FMLP and 5 micrograms/ml cytochalasin B and was assessed by measurement of eosinophil peroxidase (EPO), leukotriene C4 (LTC4) and superoxide radical (.O2-) secretion. Treatment of HE with 100 microM mepacrine before activation blocked EPO release (2.0 +/- 0.2 vs 10.2 +/- 2.1% cell content for activated HE, P < 0.004, n = 9), .O2- generation (2.6 +/- 0.9 vs 44.2 +/- 10.8 nmol/ml per 10(6) HE, P < 0.002, n = 5), and LTC4 secretion (68.2 +/- 32.2 vs 1,125.2 +/- 526.8 pg/ml per 10(6) HE, P < 0.04, n = 8). Pretreatment of HE with 100 microM 4-bromophenacyl bromide before activation similarly blocked EPO release, .O2- generation and LTC4 secretion. Addition of AA to HE after treatment with 100 microM mepacrine and before subsequent activation reversed the inhibition of both EPO (10.4 +/- 2.2% with 1 microM AA vs 2.0 +/- 0.2% for mepacrine, n = 5, P < 0.02) and LTC4 secretion (695.1 +/- 412.9 with 10 microM AA vs 68.2 +/- 32.2 pg/ml per 10(6) HE for mepacrine, n = 8, P < 0.04), but did not reverse inhibition of .O2- generation by mepacrine. We demonstrate that secretion of preformed cytotoxic proteins and .O2- by eosinophils is regulated endogenously by phospholipase A2.

Acetophenones↗

PubMed1993

Magnesium bolus or infusion fails to improve expiratory flow in acute asthma exacerbations.

HYPOTHESIS: Intravenous magnesium sulfate improves objective measures of expiratory flow in patients with acute severe exacerbations of asthma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Urban emergency department. PARTICIPANTS: Forty-eight asthmatic patients aged 18 to 60 years with initial peak expiratory flow rate (PEFR) < 200 L/min who failed to double their initial PEFR after two standardized albuterol treatments. INTERVENTIONS: Subjects were randomized to three groups: a loading dose of magnesium sulfate, 2 g IV over 20 min followed by 2 g/h over 4 h (infusion), magnesium sulfate, 2 g over 20 min followed by placebo infusion (bolus), or placebo loading dose and infusion (placebo). All subjects received standardized aminophylline and steroid therapy. MEASUREMENTS: The PEFR and FEV1 were measured at the start of the loading dose, and 20, 50, 80, 140, 200, and 260 min later using a water-displacement spirometer. Changes from baseline were compared by one-way analysis of variance for repeated measures. RESULTS: Magnesium sulfate administration did not at any time significantly improve either FEV1 (F = 0.036, p = 0.96) or PEFR (F = 0.51, p = 0.61). This study had the power to detect a PEFR difference of 26 L/min and a FEV1 difference of 0.19 L between groups (beta = 0.20, alpha = 0.05 two-tailed significance). CONCLUSION: Use of IV magnesium sulfate in addition to standard therapy does not provide clinically meaningful improvement of objective measures of expiratory flow in patients with moderate to severe asthma exacerbations.

Acute Disease↗

PubMed1992

Prazosin suppresses development of axonal damage in rats inoculated for experimental allergic encephalomyelitis.

The effectiveness of the alpha 1-adrenergic antagonist prazosin for preventing monoaminergic axonal damage in the spinal cords of rats that were inoculated for experimental allergic encephalomyelitis (EAE) was assessed using immunohistochemistry. Prazosin injections (2 mg, i.p.) given twice daily from day 7 to day 15 postinoculation significantly reduced paralysis, spinal cord inflammation and monoaminergic axonal damage compared to saline injections. A close positive correlation between severity of inflammation and severity of axonal damage was found for both prazosin- and saline-treated rats that were inoculated for EAE. These findings confirmed previous observations of suppression of the development of clinical signs of EAE by prazosin treatment and supported the hypothesis that some factor associated with spinal cord inflammation may be responsible for the bulbospinal monoaminergic axonal damage that occurs during EAE.

Animals↗

PubMed1992

Direct effects on airway smooth muscle contractile response caused by endothelin-1 in guinea pig trachealis.

Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, causes tracheal smooth muscle (TSM) relaxation followed by sustained contraction when administered intravenously in guinea pigs by a mechanism that depends upon an intact airway epithelium. To elucidate the potential role of the epithelium in modulating the response to ET-1 and the potential effects of local release of ET-1, we studied the effects of topical application of ET-1 to a segment of TSM in situ. An epithelium smooth muscle preparation that does not disrupt normal anatomic relationships was used; smooth muscle contraction was measured isometrically in vivo. Application of 10(-10) mol/cm2 ET-1 to the epithelial surface in six animals caused 2.27 +/- 0.45 g/cm active tension (AT) of the TSM segment after 30 min (p less than 0.05 versus baseline); an initial relaxation response was not observed. Endothelin-1 was dose-dependent and was 1,000 times more potent than acetylcholine in causing AT in TSM. Pretreatment with ET-1 did not alter the subsequent response to acetylcholine. Contraction elicited by topical application of ET-1 persisted greater than 3 h. In five animals in which the epithelium was removed, 10(-10) mol/cm2 ET-1 caused 4.45 +/- 0.92 g/cm AT after 30 min (p less than 0.05 versus intact epithelium). These data suggest that topical application of ET-1 elicits responses that are different from those elicited in the same preparation after intravenously administered ET-1: (1) TSM contraction that is not preceded by a transient relaxation phase, and (2) contraction that is not reduced after removal of the epithelium.

Acetylcholine↗

PubMed1992

Direct effects and augmentation of airway smooth muscle contraction caused by phospholipase A2.

We examined the effect of phospholipase A2 (PLA2; Naja naja) on isometric tracheal smooth muscle force generation in guinea pig trachealis in situ. Direct application of PLA2 to the surface of the trachea caused dose-related contraction of tracheal smooth muscle. In seven guinea pigs, a dose/density of 100 micrograms/cm2 PLA2 caused active tension (AT) that began immediately and was maximum (1.32 +/- 0.13 g/cm) at 5 min (p less than 0.01 versus baseline tension). PLA2 also augmented the contractile response to intravenously administered acetylcholine (ACh); AT caused by 3 x 10(-7) mol/kg ACh was 0.98 +/- 0.13 g/cm after PLA2 versus 0.64 +/- 0.09 g/cm in control animals (p = 0.003). PLA2 inactivated with bromophenacyl bromide (BPB) prior to topical application neither caused contraction (-0.18 +/- 0.18 g/cm AT, p = NS versus baseline tension) nor altered muscarinic responsiveness to 3 x 10(-7) mol/kg ACh. Contraction caused by 100 micrograms/cm2 PLA2 was greater after epithelium removal (2.73 +/- 0.40 g/cm AT versus 1.32 +/- 0.13 g/cm AT in epithelium-intact animals, p less than 0.005). However, epithelium removal (confirmed histologically) attenuated completely augmentation of muscarinic contraction caused by PLA2. Augmentation of muscarinic contraction also was blocked with 15 mg/kg 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW 755c), an inhibitor of eicosanoid synthesis, administered intravenously 30 min prior to topical application of 100 micrograms/cm2 PLA2. In contrast, contraction of tracheal smooth muscle caused by PLA2 was not affected significantly by blockade of eicosanoid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1992

Topographic distribution of prostaglandin secretion caused by bradykinin in canine tracheal epithelial cells.

Inflammatory mediators promote the synthesis and secretion of prostaglandin (PG) mediators in airway epithelial cells. In this study, we examined the topographic and kinetic profile of PG secretion in canine tracheal epithelial cells harvested from the tracheal posterior membrane (PM) and those obtained from the immediately anterior cartilage-associated membrane (CM). Primary cultures of tracheal epithelial cells obtained from 23 disease-free dogs were grown to confluence in serum-enriched medium. Cells then were incubated in serum-free medium for 1 h and stimulated with 10(-7) to 10(-5) M bradykinin. Baseline secretion of PGE2 was similar to both PM and CM cells; however, PM cells secreted greater concentrations in both PGI2 (measured as 6-keto-PGF1 alpha) (1,269 +/- 160 versus 775 +/- 91 pg/10(6) cells, P less than 0.01) and PGF2 alpha (436 +/- 54 versus 234 +/- 45 pg/10(6) cells, P less than 0.002) compared with CM cells. Bradykinin (BK) stimulation caused substantial secretion in less than or equal to 20 min of PGE2 and 6-keto-PGF1 alpha from PM but not CM cells: after stimulation with 10(-6) M BK, 6-keto-PGF1 alpha secretion was 348 +/- 74% in PM cells versus 157 +/- 18% of baseline secretion in CM cells (P less than 0.005); PGE2 secretion was 310 +/- 53% in PM cells versus 163 +/- 15% of baseline secretion in CM cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Oxygen metabolism and catecholamine secretion during chloralose anesthesia in lambs.

Anesthetic agents are required when restraining animals in most forms of animal research. In particular, alpha-chloralose is a widely used anesthetic for respiratory and cardiovascular research despite limited controlled studies investigating whether chloralose could represent a variable influencing cardiorespiratory reflexes in acute animal studies. We previously used a chronically-instrumented neonatal lamb model to determine that chloralose had important effects on oxygen delivery and on basal hemodynamics. To investigate the influence of chloralose on oxygen metabolism and catecholamine secretion in relation to these hemodynamic changes, we studied 12 lambs before and after infusion of chloralose (30 mg/kg, i.v.) or control saline vehicle. Chloralose caused no differences in arterial or mixed venous oxygen contents, arterio-venous oxygen difference, or oxygen delivery, consumption, or extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1991

A kinetic assay for eosinophil peroxidase activity in eosinophils and eosinophil conditioned media.

The activity of eosinophil peroxidase (EPO) is commonly employed as a measure of eosinophil activation in biologic fluids. Determination of product formation by this enzyme by end-point measurement may be affected profoundly by substrate concentrations, reaction time and degradation of end-product and enzyme. To determine more accurately EPO concentrations in media conditioned by isolated, purified eosinophils, we have developed a kinetic, colorimetric assay to measure EPO concentration as a function of maximum velocity of reaction (Vmax). An automated method for determining Vmax in a 96-well microplate colorimetric assay was utilized over a wide range of substrate concentrations. Concentrations greater than or equal to 3 x 10(-8) g/ml could be determined reliably with this assay. Peroxidase activity was inhibited in a concentration-dependent manner by the addition of 3-amino-1,2,4-triazole (AMT). The EPO concentration in eosinophils determined by this kinetic method was approximately 1.1 x 10(-5) g/10(6) eosinophils. Eosinophil activation with 10(-6) M f-Met-Leu-Phe (fMLP) caused substantial EPO secretion (9.0 +/- 1.7% vs. 2.9 +/- 0.6% total EPO content for control, P = 0.05) and decrease in eosinophil EPO concentration (92.3 +/- 4.2% of control, P = 0.038). Secretion was enhanced by the addition of 5 micrograms/ml cytochalasin B to 10(-6) M fMLP (25.9 +/- 12.7% total EPO content, P = 0.043 vs. control); similar decreases were noted in eosinophil EPO concentration (71.7 +/- 16.1% of control, P = 0.043). These data demonstrate that determination of EPO secretion by measurement of Vmax is a reliable, accurate method for precise quantification of this enzyme in media containing purified eosinophils or eosinophil products in the absence of other forms of peroxidase activity.

Amitrole↗

PubMed1991

Effects of 5-hydroxytryptophan on extracellular serotonin in the spinal cord of rats with experimental allergic encephalomyelitis.

Serotonin (5-HT) and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were collected by in vivo dialysis in the lumbar spinal cord of control rats and rats with hindlimb paralysis induced by experimental allergic encephalomyelitis (EAE). Both 5-HT and 5-HIAA were significantly decreased in baseline samples from EAE rats compared to controls. This decrease in extracellular 5-HT and 5-HIAA in the EAE rats was accompanied by marked morphological changes in spinal cord axons and axon terminal plexuses that were stained for 5-HT-like immunoreactivity. The 5-HT precursor, 5-hydroxytryptophan (5-HTP)-increased 5-HT and 5-HIAA levels in dialysate samples from both control and EAE animals. However, the 5-HTP-induced increase in extracellular 5-HT was significantly greater in the EAE rats than in the controls, despite a lower baseline 5-HT level in the EAE animals. In contrast to 5-HT, both baseline and post-5-HTP levels of 5-HIAA were significantly higher in control animals than in EAE animals. The decreased extracellular 5-HT and 5-HIAA in baseline samples from the EAE rats compared to controls is probably a consequence of the damage to descending 5-HT axons and axon terminals that occurs during the disease. The larger increase in extracellular 5-HT in EAE animals after precursor injection may reflect both decreased 5-HT reuptake from the extracellular space by damaged 5-HT terminals and disruption of the blood-brain barrier that allows entry into the central nervous system of 5-HT that was synthesized from 5-HTP in the periphery.

5-Hydroxytryptophan↗

PubMed1991

Norepinephrine effects on spinal motoneurons.

Intracellular recordings from cat spinal motoneurons in situ demonstrated that microiontophoretic application of NE with low-intensity ejection currents produces a slowly developing, small-amplitude depolarization of the cells, in contrast to early reports of NE-induced hyperpolarization. This depolarization was associated with an increase in excitability of the cells and a decrease in membrane conductance. These observations are consistent with the hypothesis that NE reduces potassium conductance in spinal motoneurons as has been proposed for facial motoneurons (VanderMaelen and Aghajanian, 1980) and thalamic neurons (McCormick and Prince, 1988). The time course of the facilitatory effects of NE on cat motoneuron excitability recorded intracellularly agreed very closely with the time course of NE-induced facilitation of glutamate-evoked excitability in rat spinal motoneurons recorded extracellularly. The similarity of the observations in rats and cats suggests that NE functions generally to enhance mammalian motoneuron responsiveness to excitatory input.

Action Potentials↗

PubMed1991

Efficacy of daily routine chest radiographs in intubated, mechanically ventilated patients.

OBJECTIVE: To determine the efficacy of daily routine chest radiographs in intubated, mechanically ventilated patients. DESIGN: With approval of our Institutional Review Board, data were collected prospectively to compare bedside clinical assessment of the patient with the routine chest radiograph in determining the occurrence of new findings. Before review of the daily chest film, patients underwent careful evaluation of clinical and physiologic variables by critical care physicians, who then documented the new findings and the diagnostic and therapeutic interventions required. These results were compared with the interpretations of the daily chest film by radiologists blinded to the clinical assessment. Correlations were made of the new major (requiring immediate intervention) and new minor (abnormal but not requiring immediate intervention) findings noted by clinical assessment and chest radiography. SETTING: This study was conducted in a ten-bed medical/surgical ICU admitting 650 to 750 patients/yr, a majority of whom require intubation and mechanical ventilation. PATIENTS: Seventy-seven episodes of intubation and mechanical ventilation in 74 patients were evaluated. Only patients with translaryngeal intubation and a requirement for mechanical ventilation beyond 24 hrs were considered for inclusion in this study. Major admitting diagnoses included malignancy, aspiration pneumonia, sepsis, liver failure, chronic obstructive pulmonary disease, and adult respiratory distress syndrome. INTERVENTIONS: Specific interventions were not made by study design; instead, clinical practice with and without the routine chest radiograph was compared. MEASUREMENTS AND MAIN RESULTS: The measure of comparison between the chest radiograph and clinical assessment was the correlation between the two for a number of major and minor findings defined in advance. A total of 538 chest radiographs were examined; of these, 354 (65.8%) did not disclose either new major or new minor findings as defined. One hundred sixty-three radiographs disclosed only new minor findings, 40.5% of which were anticipated by bedside assessment. However, in 13 (17.6%, 95% confidence interval 9% to 26%) of our 74 patients, new major findings were discovered only by chest radiography. CONCLUSIONS: These data demonstrate that, while a large percentage of radiographs will not disclose new findings, routine daily studies have a substantial impact on the management of intubated, mechanically ventilated patients in the ICU. These findings support the use of daily chest radiographs in critically ill patients.

Adolescent↗

PubMed1991

Epithelial modulation of airway smooth muscle response to endothelin-1.

We investigated the role of epithelial modulation of contraction caused by endothelin-1 in airway smooth muscle in guinea pigs in situ. Airway responses were assessed isometrically as tracheal force and simultaneously as change in lung resistance. Intravenous administration of 10(-8) mol/kg endothelin-1 caused a biphasic response in tracheal active tension: initial relaxation (-0.82 +/- 0.22 g/cm after 30 s, p less than 0.05 versus baseline) followed by contraction (1.65 +/- 0.28 g/cm after 7 min, p less than 0.05 versus baseline). Endothelin-1 also elicited immediate bronchoconstriction; lung resistance increased from 0.148 +/- 0.030 to 0.992 +/- 0.274 cm H2O/L/s (p less than 0.005) after 10(-8) mol/kg endothelin-1 given intravenously. Active tension elicited by 10(-8) mol/kg endothelin-1 after removal of the epithelium from the tracheal segment (0.59 +/- 0.16 g/cm) was less than in segments with an intact epithelium (1.65 +/- 0.28 g/cm, p less than 0.01). Both tracheal contraction and bronchoconstriction were attenuated by pretreatment with indomethacin orally, BW 755C intravenously, or substitution of endothelin-C-terminal hexapeptide for endothelin-1. However, the initial tracheal relaxation response was similar after each intervention. These data suggest actions of endothelin-1 that have not been demonstrated previously: (1) endothelin-1 elicits a biphasic response in tracheal smooth muscle (an initial relaxation response elicited by the carboxy-terminal residues and a later contractile response that requires synthesis of a cyclooxygenase mediator) and (2) epithelium adjacent to the airway smooth muscle modulates contraction elicited by endothelin-1.

Animals↗

PubMed1990

Damage to bulbospinal serotonin-, tyrosine hydroxylase-, and TRH-containing axons occurs early in the development of experimental allergic encephalomyelitis in rats.

Spinal cord monoaminergic and peptidergic axonal damage occurring during the development of experimental allergic encephalomyelitis (EAE) was assessed using immunohistochemistry. Spinal cord axons immunoreactive for serotonin, catecholamines, or a thyrotropin-releasing hormone marker peptide were found to be markedly swollen and distorted by the earliest stage of detectable paralysis during EAE development (the flaccid tail stage). As clinical signs progressed to complete hindlimb paralysis, axonal damage became increasingly extensive. Axonal damage was equally pronounced whether EAE was induced by inoculation with purified myelin basic protein or with whole spinal cord homogenate, suggesting that the damage did not result from an immune attack directed against specific monoaminergic and/or peptidergic antigens present in the inoculant. However, two observations suggested that mechanical or chemical factors associated with the inflammatory foci contribute to the axonal damage: first, distorted axons were nearly always located adjacent to blood vessels or the pial surface, sites at which inflammation occurs during EAE. Second, the severity of axonal damage correlated with the severity of the inflammation. The early onset of axonal damage during development of EAE and the close correlation that was found between the severity of axonal damage and the severity of clinical signs suggested that the axonal damage may contribute to the clinical signs of the disease.

Animals↗