Toxic encephalopathy due to 1,1,1-trichloroethane.
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Adult↗
Biomedical subjects
R A Berg
Publications and source records attributed to R A Berg.
Regulation of collagen synthesis in human dermal fibroblasts by the sodium and magnesium salts of ascorbyl-2-phosphate.
Ascorbic acid has been shown to stimulate collagen synthesis in dermal fibroblasts by increasing the rate of transcription of collagen genes. Experiments involving the use of ascorbic acid require daily supplementation due to the instability of the molecule in aqueous solutions. In order to provide a more stable alternative to ascorbic acid, two salts of ascorbyl-2-phosphate, having a greater chemical stability than ascorbic acid, were tested for their ability to stimulate collagen synthesis in monolayer fibroblast cultures. The concentration and time dependence of their activities were compared with ascorbic acid. The magnesium salt of ascorbyl-2-phosphate was found to be equivalent to ascorbic acid in stimulating collagen synthesis in these assays, while the sodium salt required at least a tenfold greater concentration to produce the same effect as ascorbic acid. Solutions of either ascorbic acid or the ascorbyl-2-phosphate analogs (at 10 mM) in phosphate-buffered saline (PBS) were relatively stable as shown by their decay rates and their ability to stimulate collagen synthesis even after nine days in solution prior to testing their effects on cultured cells. Ascorbic acid was unstable at neutral pH compared to solutions of either sodium or magnesium ascorbyl-2-phosphate. These data support the use of magnesium ascorbyl-2-phosphate in experiments where stability of ascorbic acid is a concern, e.g. in long-term cultures or in in vivo studies.
Ascorbic Acid↗
Bystander cardiopulmonary resuscitation. Is ventilation necessary?
BACKGROUND: Prompt initiation of bystander cardiopulmonary resuscitation (CPR) improves survival. Basic life support with mouth-to-mouth ventilation and chest compressions is intimidating, difficult to remember, and difficult to perform. Chest compressions alone can be easily taught, easily remembered, easily performed, adequately taught by dispatcher-delivered telephone instruction, and more readily accepted by the public. The principal objective of this study was to evaluate the need for ventilation during CPR in a clinically relevant swine model of prehospital witnessed cardiac arrest. METHODS AND RESULTS: Thirty seconds after ventricular fibrillation, swine were randomly assigned to 12 minutes of chest compressions plus mechanical ventilation (group A), chest compressions only (group B), or no CPR (group C). Standard advanced cardiac life support was then provided. Animals successfully resuscitated were supported for 2 hours in an intensive care setting, and then observed for 24 hours. All 16 swine in groups A and B were successfully resuscitated and neurologically normal at 24 hours, whereas only 2 of 8 group C animals survived for 24 hours (P < .001, Fisher's exact test). One of the 2 group C survivors was comatose and unresponsive. CONCLUSIONS: In this swine model of witnessed prehospital cardiac arrest, the survival and neurological outcome data establish that prompt initiation of chest compressions alone appears to be as effective as chest compressions plus ventilation and that both techniques of bystander CPR markedly improve outcome compared with no bystander CPR.
Animals↗
Dobutamine pharmacokinetics and pharmacodynamics in normal children and adolescents.
Pharmacokinetic and pharmacodynamic data on adrenergic agents in children have revealed wide ranges of plasma clearance rates and hemodynamic responses in patients with critical illnesses or myocardial dysfunction. In order to more clearly elucidate the underlying pharmacologic processes, graded i.v. dobutamine infusions of 0.5, 2.5 and 5.0 micrograms/kg/min were sequentially administered to healthy children and adolescents. Plasma dobutamine concentrations and hemodynamic responses, including echocardiographic measures of systolic and diastolic function, were determined at each infusion rate. Pharmacodynamic data were evaluated by both threshold modeling and mean hemodynamic responses to each infusion rate. Mean plasma dobutamine clearance was 115 +/- 63 ml/kg/min, with an intersubject variability greater than 5-fold. These data establish that the previously published wide variability in dobutamine clearance is not due simply to underlying disease states. Dobutamine clearance was linear over the dosage range evaluated. Dobutamine improved systolic function even at plasma concentrations attained with infusion rates as low as 1 to 2 micrograms/kg/min. The improved systolic function was at least partially due to inotropic effects. In addition, dobutamine improved diastolic function and reduced afterload. Chronotropic effects were observed in only two subjects and only at higher plasma concentrations than the other hemodynamic effects. Individualized threshold modeling effectively described the log-linear relationship between plasma dobutamine concentration and hemodynamic response beyond the threshold concentration.
Adolescent↗
Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema.
Transgenic mice were generated that expressed a human collagenase transgene in their lungs under the direction of the haptoglobin promoter. Histological analysis demonstrated disruption of the alveolar walls and coalescence of the alveolar spaces with no evidence of fibrosis or inflammation. This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process. Although elastase has been proposed as the primary enzyme responsible for emphysematous lung damage, this study provides evidence that other extracellular matrix proteases could play a role in emphysema. In addition, these transgenic mice are a defined genetic animal model system to study the pathogenesis of emphysema.
Animals↗
Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.
Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Accuracy of central venous pressure monitoring in the intraabdominal inferior vena cava: a canine study.
STUDY OBJECTIVE: To test the hypotheses that in multiple pathophysiologic settings (1) end-expiratory central venous pressure measurements in the intraabdominal inferior vena cava accurately reflect those in the superior vena cava and (2) mean central venous pressure monitoring is as reliable in the inferior vena cava as it is in the superior vena cava. DESIGN: Simultaneous inferior vena caval and superior vena caval pressures were measured during five ventilatory phases: apnea, end-expiratory mechanical ventilation, maximal inspiratory mechanical ventilation, end-expiratory spontaneous ventilation, and maximal inspiratory spontaneous ventilation. Measurements were repeated after progressive intravascular volume depletion. SUBJECTS: Eight puppies. MEASUREMENTS AND RESULTS: Simultaneous inferior vena caval and superior vena caval end-expiratory pressures did not differ significantly (mean differences 0 to 0.1 mm Hg) and the limits of agreement of these measurements were within 2 mm Hg. Differences between mean maximal inspiratory pressures in the inferior vena cava and superior vena cava during mechanical and spontaneous ventilation were -0.7 and 3.6 mm Hg, respectively (p less than 0.01), and the limits of agreement extended beyond 2 mm Hg. Furthermore, mean maximal inspiratory pressures in the superior vena cava differed from end-expiratory pressures in the superior vena cava (1.1 and -3.6 mm Hg, p less than 0.01), whereas those in the inferior vena cava did not differ from end-expiratory superior vena caval pressures. CONCLUSIONS: Under the experimental conditions studied (1) end-expiratory intraabdominal inferior vena caval pressures accurately reflected end-expiratory superior vena caval pressures and (2) mean central venous pressure monitoring was as reliable in the inferior vena cava as in the superior vena cava.
Abdomen↗
Nutritional aspects of collagen metabolism.
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Amino Acids↗
Neuropsychological performance and suicidal behavior in adult psychiatric inpatients.
Although various studies have shown that suicidal persons exhibit greater cognitive deficiencies than both normals and other psychiatric patients, researchers as yet have been unable to account for the source(s) of the differences. Some of these differences (e.g., cognitive rigidity and impaired problem solving) hint of possible organic involvement. This study explored the relationship of neuropsychological functioning to suicidal behavior by comparing 20 suicidal and 27 nonsuicidal psychiatric inpatients on several tests of neuropsychological functioning. Although results showed no significant differences between the two groups on most measures, both groups showed evidence of notably high levels of cortical dysfunction relative to test norms. Thirty-five percent of suicidal patients and 44% of nonsuicidal patients scored in the impaired range. Implications of this high frequency of impairment for the treatment of suicidal and nonsuicidal psychiatric patients are discussed.
Adult↗
Revised norms and decision rules for the Luria-Nebraska Neuropsychological Battery, Form II.
All control subjects from a previous Luria-Nebraska Neuropsychological Battery, Form II (LNNB2) normative study were combined with a considerably larger normative sample to produce a composite normative sample of 392 subjects with a mean high school educational level. Revised norms for the LNNB2 were developed based on this sample and were scaled with uniform T-scores to make scale elevations comparable across LNNB2 measures. Differences between the scalewise LNNB2 normative values and published alternatives were highly significant. A critical level and actuarial decision rules for differentiation of normal from neurologically impaired performance level were developed for the LNNB2 using the current empirical norms (86% accuracy with current sample empirical critical level; 89% accuracy with LNNB1 critical level). The normative prediction values of Golden, Purisch, and Hammeke for the LNNB2 were not satisfactory (69% overall, with 45% accuracy among brain damaged sample). There was no significant effect of sex of subject on LNNB2 performance level among the control subjects.
Journal Article↗
Accuracy of central venous pressure measurement from the abdominal inferior vena cava.
Central venous pressure measurements in the abdominal inferior vena cava were compared with measurements in the right atrium in 10 infants and 10 children during cardiac catheterization. At end expiration, the mean pressures at these two sites were within 1 mm Hg of each other in all 20 patients, with a mean difference of 0.0 +/- 0.36 mm Hg. The abdominal inferior vena cava is a safe and convenient site for measurement of central venous pressure, and our study confirms that such measurements are accurate.
Adolescent↗
A novel 53-kDa polypeptide from chicken embryo.
We have isolated from chicken embryos a novel 53-kDa protein possessing properties which are similar, but not identical to the 55-kDa PDI polypeptide from chicken embryos. The novel 53-kDa polypeptide copurifies with PDI, but is separated by ion-exchange chromatography. The novel 53-kDa polypeptide cross-reacts strongly with antibodies specific for bovine PDI and cross-reacts to varying degrees with six different preparations of antibodies specific for chicken PDI which is identical to the beta-subunit of chicken prolyl 4-hydroxylase. Anti-bovine PDI immunoglobulins selected by the purified 53-kDa polypeptide react with bovine PDI but not with the beta-subunit of prolyl 4-hydroxylase, suggesting that the 53-kDa polypeptide shares epitopes with bovine PDI but not with the chicken prolyl 4-hydroxylase beta-subunit. Amino acid compositional analysis of the purified polypeptide yielded unique data when compared to PDI and other PDI-like polypeptides. Edman degradation from the N terminus of the 53-kDa polypeptide yields a sequence very different from the N terminus of PDI. This sequence is unique when compared to all entries in available databases. A 20-residue sequence of an internal cyanogen bromide fragment of the 53-kDa polypeptide gives a nearly identical match with human beta-endorphin. The 53-kDa polypeptide is capable of cleaving the disulphides of insulin under conditions where PDI is active. The periodic acid-Schiff assay failed to detect bound carbohydrate. These observations support evidence for a family of PDI-like proteins in chicken embryo and suggest that PDI activity is not confined to only one protein.
Amino Acid Sequence↗
Modulation of collagen synthesis by growth factors: the role of ascorbate-stimulated lipid peroxidation.
Ascorbic acid has been shown to stimulate collagen synthesis through induction of lipid peroxidation leading to increased transcription of the collagen genes. The mechanism by which lipid peroxidation stimulates collagen transcription is unknown; however, an alteration of cell membranes may affect the activity of serum growth factors leading to a change in gene expression. To test this hypothesis, we treated dermal fibroblasts with transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), interleukin-1 (IL-1), platelet-derived growth factor (PDGF), or fibroblast growth factor (FGF) in the presence of lipid peroxidation stimulating (200 microM) and nonstimulating (1 microM) concentrations of ascorbic acid. EGF and IL-1 had no effect on collagen synthesis at either concentration of ascorbic acid. FGF affected collagen synthesis only in the presence of 200 microM ascorbic acid, producing both a stimulation (0.4-2 ng/ml) and an inhibition (greater than 50 ng/ml). PDGF and TGF-beta stimulated collagen synthesis in the presence of both concentrations of ascorbic acid, with TGF-beta producing an 11-fold increase in collagen synthesis in the presence of ascorbate. This synergism produced by the combination of ascorbic acid and TGF-beta was inhibitable by the lipid peroxidation inhibitor, propyl gallate. These results indicate that regulation of collagen synthesis by ascorbic acid does not occur through altering the response to EGF or Il-1. Ascorbate has no effect on PDGF but the effects of TGF-beta and FGF on collagen synthesis appear to be sensitive to lipid peroxidation.
Ascorbic Acid↗
Correlation of the steady-state RNA levels among the alpha-subunit of prolyl 4-hydroxylase and the alpha 1 and alpha 2 chains of type I collagen during growth of chicken embryo tendon fibroblasts.
The relative steady-state levels of RNAs encoding type I collagen and prolyl 4-hydroxylase were examined in exponentially growing primary cultures of chicken embryo tendon fibroblasts. The RNA levels of the alpha 1 and alpha 2 chains of type I collagen were maximal when the fibroblasts reached the confluent state. The RNA levels of the alpha-subunit of prolyl 4-hydroxylase were also maximal at confluency and rose and fell with the RNA levels of the two collagen chains. The RNA levels of the beta-subunit of prolyl 4-hydroxylase did not correlate with the changes observed for the alpha-subunit or for either chain of type I collagen. The RNA levels of the beta-subunit were slightly higher than the RNA levels of the alpha-subunit. These results support our hypothesis that the synthesis of the alpha-subunit and thus the association of newly synthesized alpha-subunits with pre-existing beta-subunits is the rate-limiting factor in determining prolyl 4-hydroxylase activity in cultured cells.
Animals↗
Bacterial tracheitis as a complication of endotracheal intubation.
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Humans↗
Neutrophil collagenase activation: the role of oxidants and cathepsin G.
The events leading to neutrophil collagenase activation in vivo were analyzed using phorbol myristate acetate (PMA) stimulated neutrophil supernatant. Under the conditions when this supernatant was incubated with the serine proteinase inhibitor, phenylmethylsulfonyl fluoride (PMSF), and then treated with the oxidant, hypochlorous acid (HOCl), collagenase was activated. When cathepsin G, a known activator of neutrophil collagenase, was also present, less HOCl was required to activate the latent collagenase. These experiments support the conclusion that activation of neutrophil collagenase occurs in vivo by both an oxidant and an enzymatic mechanism where the effectiveness of oxidants is enhanced by cathepsin G.
Cathepsin G↗
Regulation of collagen synthesis by ascorbic acid: characterization of the role of ascorbate-stimulated lipid peroxidation.
Recently, we have described the ability of traditional lipid peroxidation inhibitors to inhibit ascorbate-stimulated collagen synthesis. In order to characterize further this effect, we have tested the ability of known and potential inhibitors of lipid peroxidation for their effects on ascorbate-stimulated collagen synthesis and lipid peroxidation. In our experiments, mannitol, a water soluble antioxidant, had no effect on ascorbate-induced collagen synthesis nor on lipid peroxidation. However, alpha-tocopherol, which is a lipophilic antioxidant, inhibited both effects of ascorbate. Superoxide dismutase, catalase, and their polyethylene glycol conjugate forms did not inhibit the ascorbate-stimulated collagen synthesis or lipid peroxidation. In addition, no effect was seen with the oxygen radical scavengers isopropanol, ethanol, or dimethyl sulfoxide. Two iron chelators, o-phenanthroline and alpha,alpha-dipyridyl, both inhibited ascorbate-induced lipid peroxidation and collagen synthesis, consistent with the previously described iron-dependence of lipid peroxidation by ascorbate. These results support a correlation between collagen synthesis and lipid peroxidation and provide a theory for the mechanism of ascorbic acid regulation of collagen synthesis.
Antioxidants↗
Thermal laser assisted balloon angioplasty in lower extremity occlusive disease.
Results of Nd:Yag thermal laser assisted balloon angioplasty (LABA) in lower extremity occlusive disease were reviewed retrospectively in 23 patients and 28 lesions over a 1 year period. Indications for intervention were progressive claudication in 74 per cent and gangrene and/or rest pain in 26 per cent. Twenty-four (86%) procedures were technically successful; however, there were only 15 (54%) clinical successes during the follow-up period (0.5-12.5 months). Complications occurred following ten (36%) procedures with one mortality (4%) unrelated to the procedure. Analysis of the nature and location of the lesions revealed five angiographic patterns with varying degrees of success. These are: Superficial Femoral and Popliteal: 1) short segment stenosis--2/3, 2) long multisegment stenosis--1/6, 3) total occlusion--7/9, 4) stenosis and occlusion--2/4; Iliac: 5) stenosis--3/4. The only subsets of patients who appeared to benefit from LABA were those with short segment stenosis or isolated occlusions. Patients with good runoff also did well. Patients with poor runoff or multiple stenoses associated with diffuse disease did poorly. It is concluded that LABA has limited applications in the treatment of lower extremity occlusive disease.
Adult↗