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Biomedical subjects

R E Stafford

Publications and source records attributed to R E Stafford.

At least 19 recordsLinked to original sources
PubMed1999

Oral contrast solution and computed tomography for blunt abdominal trauma: a randomized study.

HYPOTHESIS: Oral contrast solution (OC) is unnecessary in the acute computed tomographic (CT) evaluation of the patient with blunt abdominal trauma. DESIGN: Randomized controlled clinical trial. SETTING: Level I trauma center at a university-affiliated teaching hospital. PATIENTS: Five hundred adult patients sustaining blunt abdominal trauma and requiring urgent resuscitation and CT evaluation of the abdomen were eligible for the study. Those patients who were younger than 18 years, pregnant, or in police custody were excluded. One hundred six patients were excluded from the analysis (15 for inappropriate enrollment, 9 because a CT scan had not been performed, 1 owing to inability to accept a nasogastric tube, and 81 owing to missing or incomplete records). Three hundred ninety-four patients with an average age of 36 years, an average Revised Trauma Score of 10, and an average Glasgow Coma Scale score of 12 are included in the analysis. INTERVENTIONS: Patients were randomized via computer-generated assignment to 1 of 2 groups either receiving OC or not receiving OC (no OC) after placement of a nasogastric tube. All patients received intravenous contrast solution and then underwent helical CT scan of the abdomen and pelvis using the GE HiSpeed Advantage CT scanner (GE Medical Systems, Milwaukee, Wis). MAIN OUTCOME MEASURES: Abnormal CT results, need for laparotomy, missed gastrointestinal tract and solid organ injuries, nausea, and vomiting. RESULTS: There were 199 patients in the OC group and 195 patients in the no OC group. Vomiting occurred in 12.9% of patients and the incidence was not different between groups. One hundred five abnormal scans (50 OC and 55 no OC) were obtained and 33 patients with abnormal scans (19 OC and 14 no OC) underwent laparotomy. There was 1 nontherapeutic laparotomy in each group. There was 1 missed small-bowel injury in the OC group (sensitivity, 86%) and no missed small-bowel injuries in the no OC group (sensitivity, 100%). Six bowel injuries were identified at laparotomy in the OC group. Two of the injuries were perforations without contrast extravasation but with pneumoperitoneum in 1. Three bowel injuries were identified in the no OC group, none of which were perforations. Seven of the 9 patients with bowel injury at laparotomy had associated intra-abdominal injury. Specificity for solid organ injury was 94% in the OC group and 57.1% in the no OC group. Sensitivity for solid organ injury was 84.2% in the OC group and 88.9% in the no OC group. The average time to abdominal CT scanning after placement of a nasogastric tube was 39.02+/-18.73 minutes in the no OC group and 45.92+/-24.17 minutes in the OC group (P= .008). CONCLUSION: The addition of OC to the acute CT protocol for the evaluation of the patient with blunt abdominal trauma is unnecessary and delays time to CT scanning.

Abdominal Injuries↗
PubMed1999

Treatment of occult pneumothoraces from blunt trauma.

BACKGROUND: Occult pneumothoraces (OPTXs) are seen on abdominal computed tomographic (CT) scans but not on routine chest x-ray films. Optimal treatment for blunt trauma OPTXs has not been defined. We hypothesized that OPTXs could be safely observed without need for a chest tube (CT). METHODS: A prospective trial randomized blunt trauma patients with OPTXs to CT scan or observation. Patients were not excluded for positive pressure ventilation. Primary outcome measures were respiratory distress and pneumothoraces progression. RESULTS: Thirty-nine patients with 44 pneumothoraces were enrolled. Eighteen patients received a CT scan, and 21 patients were observed. Nine patients in each group received positive pressure ventilation. There was no difference in overall complication rate. No patient had respiratory distress related to the OPTX or required emergent CT scan. CONCLUSIONS: Observation of OPTX is not associated with an increased incidence of pneumothorax progression or respiratory distress. These pneumothoraces can be safely observed in patients with blunt trauma injury regardless of the need for positive pressure ventilation.

Adult↗
PubMed1998

Incidence and significance of free fluid on abdominal computed tomographic scan in blunt trauma.

OBJECTIVE: To determine the incidence and significance of free fluid on abdominal CT in blunt trauma. DESIGN: Retrospective chart review. METHODS: All blunt trauma patients with an abdominal computed tomographic scan from August of 1993 to December of 1995 were identified from the trauma registry at a Level 1 trauma center. A total of 1,159 computed tomographic scans were performed; records of 18 patients were excluded for incomplete records. Official reports of computed tomographic scans were reviewed for free fluid, solid organ injury, bladder injury, and pelvic fracture. RESULTS: Free fluid without solid organ injury was found in 3% (34 of 1141). Laparotomy was performed because of free fluid in 13 patients. There were six small bowel injuries and one diaphragm injury for a therapeutic laparotomy rate of 54%. Ten patients had trace free fluid and did not undergo laparotomy; none had a missed small bowel injury. CONCLUSIONS: The presence of more than trace amounts of free fluid without solid organ injury in patients with blunt trauma is a strong indication for exploratory laparotomy. Patients with isolated trace amounts of free fluid can be safely observed.

Abdominal Injuries↗
PubMed1997

Marked alterations in circulating inflammatory cells during cardiomyopathy development in a magnesium-deficient rat model.

Rodents fed on a Mg-deficient (Mg-D) diet develop cardiomyopathic lesions, as well as other types of cardiovascular dysfunction. In the rat, inflammatory cell infiltration of the myocardium begins to occur by week 1, and the lesions develop extensively in the third and fourth weeks on the Mg-D diet. Although the aetiologic mechanisms of Mg-D cardiomyopathy are unknown, we have previously reported that once plasma Mg is markedly reduced, one of the earliest molecular markers of the pathophysiological process is elevation of plasma substance P, calcitonin gene-related peptide and prostaglandin E2, followed by histamine and the inflammatory cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha). In order to evaluate the potential role of specific circulating inflammatory cell subpopulations in the mechanisms underlying pathophysiological changes observed in Mg-deficiency-induced cardiomyopathy, we analysed these cells by flow cytochemistry. Leucocyte subpopulation pools increased progressively in the Mg-D rats. Elevated circulating levels of neutrophils and lymphocytes appeared to contribute to both the acute (week 1-2) and chronic phases (week 3-4) of the inflammatory responses; monocytes, eosinophils, basophils and large unstained cells which are lymphoid in stained smears, on the other hand, increased significantly in the third and fourth weeks and thus contributed to the chronic inflammatory phase. Changes in the circulating leucocyte subpopulations paralleled the chronological progression of the cardiomyopathic lesions, particularly in weeks 3 and 4. Since a pronounced neutrophilia preceded leucocyte infiltration and deposition within the myocardial tissue, modifications of the microvascular barrier may be a prerequisite for cardiomyopathy in this model of neurogenic inflammation.

Acute Disease↗
PubMed1996

Enhanced NO production during Mg deficiency and its role in mediating red blood cell glutathione loss.

The effect of dietary Mg deficiency on nitric oxide (NO) production and its role in mediating oxidative depletion of red blood cell (RBC) glutathione in rats were investigated. Male Sprague-Dawley rats were placed on Mg-deficient or Mg-sufficient diets for up to 3 wk. Plasma nitrate plus nitrite levels, determined by the Escherichia coli reductase/Griess reagent procedures, increased 1.7-fold during the 1st wk and increased 2- to 2.4-fold during the 2nd and 3rd wk on the Mg-deficient diet. In association, substantial losses (approximately 50%) of RBC glutathione occurred during the 2nd and 3rd wk. Administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in drinking water (0.5 mg/ml) effectively blunted the increases in plasma nitrate/nitrite during Mg deficiency. Concomitantly, losses of RBC glutathione exhibited by Mg-deficient rats were significantly attenuated. Packed RBCs, obtained from Mg-deficient but not from Mg-sufficient animals, displayed a prominent nitrosyl hemoglobin signal detected by electron spin resonance spectroscopy; the signals of the samples from the L-NAME-treated Mg-deficient rats were greatly reduced. With isolated RBCs, losses of the glutathione could be induced directly by peroxynitrite or 3-morpholinosydnonimine, which generates NO + .O2-, but not by NO (from sodium nitroprusside) alone, in a concentration-dependent manner. The results clearly indicate that NO overproduction occurs and participates in RBC glutathione loss during Mg deficiency. Because neutrophil activation also occurs, we suggest that NO might interact with superoxide anions to form peroxynitrite, which then directly oxidizes RBC glutathione.

Animals↗
PubMed1994

Neurogenic peptides and the cardiomyopathy of magnesium-deficiency: effects of substance P-receptor inhibition.

Dietary deficiency of magnesium (Mg) in rodents results in cardiomyopathic lesion formation. In our rat model, these lesions develop after 3 weeks on the Mg-deficient diet; significant elevation of several cytokines, IL-1, IL-6 and TNF alpha also occurs. In probing the mechanisms of lesion formation, we obtained data supporting the participation of free radicals (Freedman AM et al.: Bioch Biophys Res Commun 1990; 170: 1102). Recently, we identified an early elevation of circulating substance P and proposed a role of neurogenic peptides during Mg-deficiency (Weglicki WB, Phillips TM: AM J Phys 1992;262:R734). The present study was designed to evaluate the contribution of neurogenic peptides to the pathogenesis of Mg-deficiency. In the blood, substance-P and calcitonin gene related peptide (CGRP) are elevated during the first week on the diet. During the second week, circulating histamine, PGE2 and TBAR-materials were elevated and red cell glutathione was reduced, all prior to the elevation of the inflammatory cytokines during the third week. When the rats were treated with the substance P-receptor blocker [CP-96,345], the levels of substance P and CGRP remained elevated; however, increases in histamine, PGE2, TBAR-materials, and the decrease in red cell glutathione were inhibited; also, the development of cardiac lesions was inhibited significantly. These data support a central role for neurogenic peptides, especially substance P, in the development of cardiomyopathic lesions during Mg-deficiency.

Animals↗
PubMed1993

Inhibition of tumor necrosis factor-alpha by thalidomide in magnesium deficiency.

The effect of thalidomide on circulating cytokines and myocardial lesion formation was investigated in Mg-deficient rats. After two weeks on a Mg-deficient diet, rats show an increase in circulating levels of tumor necrosis factor-alpha and interleukin 1. Thalidomide (1 mg/day) caused a complete inhibition of the increase in circulating tumor necrosis factor-alpha levels, without having an effect on interleukin 1. However, a marked increase in cardiomyopathic lesion formation was observed in Mg-deficient animals treated with thalidomide; possible mechanisms for thalidomide's enhancement of myocardial injury are discussed.

Animals↗
PubMed1993

Protein oxidation in magnesium deficient rat brains and kidneys.

Magnesium deficiency produces a pro-oxidant systemic inflammation in rats. The purpose of these experiments was to determine if and when there is any oxidation of cellular proteins. We have found there is a significant increase in protein oxidation products, protein carbonyls, in both the brain and the kidney within 2 to 3 weeks on a magnesium deficient diet. These changes occur prior to any detectable changes in cellular glutathione, tissue damage or dysfunction. We conclude that oxidation of cellular proteins occur early in magnesium deficiency and may contribute to the tissue damage and loss of function observed in the later stages of the deficiency. This is the first demonstration of the time course of protein oxidation product development in magnesium deficient animals.

Animals↗
PubMed1993

Kinetic analysis and substrate specificity of a lysophospholipase from the macrophage-like cell line P388D1.

The kinetics of the lysophospholipase purified from the P388D1 macrophage-like cell line (Zhang and Dennis (1988) J. Biol Chem. 263, 9965-9972) have been explored. Three different lysophospholipids were used in these studies: 1-hexadecanoyllysophosphatidylcholine, 1-tetradecanoyllysophosphatidylcholine, and 1-hexadecanoyllysophosphatidylglycerol. Since all of the substrate dependence data for these substrates fit a Hill model, the enzyme's activity appears to be cooperative requiring at least two lipid molecules for full enzymatic activity. The enzyme did not show a preference for any of these substrates since their kcat ranged from 1.2 to 1.5 mumol min-1 mg-1 and their half-maximal activities ([S]0.5) were achieved at substrate concentrations between 15 and 33 microM. Enzymatic activity also appeared to be independent of the aggregation state of the substrate. No dramatic changes in rate could be associated with substrate aggregation at the critical micelle concentration. This is in marked contrast to some phospholipases A2 that exhibit dramatic activations when their substrates aggregate. In very dilute solutions, less than 0.5 micrograms/ml protein, the lysophospholipase loses activity irreversibly within minutes. This effect of low protein concentrations can be overcome by maintaining the enzyme in the presence of greater than 10 microM lysophospholipid. This inactivation can affect kinetic studies, since the [S]0.5s for this enzyme are usually in this range. We have found that increasing the protein concentration with a 'non-specific protein', e.g., cytochrome c, can protect the enzyme without affecting activity and, thus, allow valid kinetic data to be obtained over the full substrate concentration range.

Animals↗
PubMed1993

Reactions of captopril and epicaptopril with transition metal ions and hydroxyl radicals: an EPR spectroscopy study.

In the present study, using the technique of EPR spin trapping with DMPO a spin trap, we demonstrated formation of thiyl radicals from thiol-containing angiotensin converting enzyme (ACE) inhibitor captopril (CAP) and from its stereoisomer epicaptopril (EPICAP), a non-ACE inhibitor, in the process of .OH radical scavenging. Splitting constants of DMPO/thiyl radical adducts were identical for both thiols and were aN = 15.3 G, and aH = 16.2 G. Bimolecular rate constants for the reaction of CAP and EPICAP with .OH radicals were close to a diffusion-controlled rate (approximately 2 x 10(10) M-1s-1). Our data also show that both CAP and EPICAP reduce Fe(III) ions and that their respective thiyl radicals are formed in this reaction. In the presence of Fe(III), H2O2, and CAP, or EPICAP, .OH radicals were produced by a thiol-driven Fenton mechanism. Copper(II) ions were also reduced by these thiols, but no thiyl radicals could be detected in these reactions, and no .OH or other Fenton oxidants were observed in the presence of H2O2. Our data show direct evidence that thiol groups of CAP and EPICAP are involved in scavenging of .OH radicals. The direct .OH radical scavenging, together with the reductive "repair" of other sites of .OH radical attack, may contribute to the known protective effect of CAP against ischemia/reperfusion-induced arrhythmias. The formation of reactive thiyl radicals in the reactions of the studied compounds with .OH radicals and with Fe(III) ions may play a role in some of the known adverse effects of CAP.

Captopril↗
PubMed1993

Modulation of cytokines and myocardial lesions by vitamin E and chloroquine in a Mg-deficient rat model.

Antioxidant treatment with alpha-tocopherol did not affect the level of the "inflammatory cytokines" in Mg-deficient animals, although it diminished the extent of the myocardial lesions. In another group of Mg-deficient animals chloroquine treatment diminished significantly the levels of circulating cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) and also resulted in a major decrease in myocardial lesions. These results raise the question of the role of these inflammatory cytokines in the formation of lesions in Mg-deficient myocardium. Because these cytokines are able to stimulate free radical production in various cell types, we postulate that Mg deficiency involves free radical mechanisms that can be amplified by inflammatory cytokines; whether these cytokines initiate lesion formation is unclear. Although our data do not confirm either possibility, we submit that these results implicate a role for the inflammatory cytokines in the cardiac pathology of Mg deficiency.

Animals↗
PubMed1992

Erythrocytes from magnesium-deficient hamsters display an enhanced susceptibility to oxidative stress.

Previous studies in our laboratory have indicated a role for free radical participation in magnesium deficiency cardiomyopathy. We have demonstrated the ability of various antioxidant drugs and nutrients to protect against magnesium deficiency-induced myocardial injury. In this study, we have examined erythrocytes from normal and magnesium-deficient animals and compared their susceptibility to an in vitro oxidative stress. Syrian male hamsters were placed on either magnesium-deficient or magnesium-supplemented diets. Animals from each group also received vitamin E in doses of 10 and 25 mg as subcutaneous implants. Erythrocytes obtained after 14 days on the diet were exposed to an exogenous hydroxyl (.OH) radical generating system (dihydroxyfumarate not equal to Fe3+ ADP) at 37 degrees C for 20 min. Erythrocyte crenation was observed and quantified by scanning electron microscopy. Lipid peroxidation, hemolysis (%), and intracellular glutathione levels were determined. In addition, serum lipid changes and membrane phospholipids were characterized. Our data demonstrate that erythrocytes from magnesium-deficient animals are more susceptible to free radical injury, supporting our hypothesis that magnesium deficiency reduces the threshold antioxidant capacity.

Adenosine Diphosphate↗
PubMed1989

Interfacial properties and critical micelle concentration of lysophospholipids.

The critical micelle concentration (cmc) of several lysophospholipids and of a lysophospholipid analogue was determined from surface tension measurements using the maximum bubble pressure method and/or 31P NMR. The use of the maximum bubble pressure method has now been extended to micromolar concentrations of surfactant, and the experimental parameters that effect its use have been explored. Surface activity was found to vary with changes in the chain length and in the headgroup polarity of the lysophospholipid. The cmc's for 1-decanoyl-, 1-dodecanoyl-, 1-tetradecanoyl-, and 1-hexadecanoyl-sn-glycero-3-phosphocholine are 7.0, 0.70, 0.070, and 0.007 mM, respectively. The cmc's for 1-decanoyl- and 1-dodecanoyl-sn-glycero-3-phosphoethanolamine are 4.4 and 0.33 mM, respectively. The cmc for dodecylphosphocholine, a lysophospholipid analogue, was found to be 1.1 mM. The cmc's for 1-tetradecanoyl- and 1-hexadecanoyl-sn-glycero-3-phosphoglycerol were found to be 3.0 and 0.60 mM, respectively, in pure water. In 0.1 M Tris-HCl (pH = 8.0), their cmc's are 0.16 and 0.018 mM, respectively. Surface tension and adsorption density values determined at the cmc are reported for each compound. The relationship of dynamic surface tension and lipid purity is discussed. These studies provide information about the micellization and interfacial properties of several biologically important lysophospholipids.

Adsorption↗
PubMed1986

The influence of preadsorbed canine von Willebrand factor, fibronectin and fibrinogen on ex vivo artificial surface-induced thrombosis.

We have examined the effects of preadsorption of several canine plasma proteins on surface-induced thrombogenesis in a canine ex vivo model. Our technique allowed determination of initial deposition and subsequent embolization of 51Cr-labeled platelets and 125I-fibrinogen onto and from polymeric arterio-venous shunts in non-anticoagulated canines. Segments of the tubing were removed at various time points between 2 and 120 minutes of blood contact for examination of the morphology of the thrombus by scanning electron microscopy. Thrombus deposition was measured on uncoated plasticized poly(vinyl chloride) (PVC) and PVC precoated with canine von Willebrand factor (vWF), fibronectin, partially purified fibrinogen (fibrinogen which contained vWF and fibronectin as impurities), or purified fibrinogen (fibrinogen which had been further purified to remove fibronectin and vWF). Preadsorption of all proteins studied enhanced the thrombogenic response relative to that of the uncoated surface. Precoating with vWF or partially purified fibrinogen resulted in the deposition of the greatest number of thrombi, and embolization was slower than on shunts precoated with canine fibronectin or purified fibrinogen. The deposition-embolization profiles for the fibronectin and purified fibrinogen-coated surfaces were similar. The amount and time sequence of initial adhesion and spreading of platelets was related to the extent and time sequence of peak thrombus formation. The partially purified fibrinogen-coated and vWF-coated surfaces had more adhered and spread platelets at the earliest time points and a greater number of larger thrombi at the peak deposition times. The slowest rate of platelet adhesion and spreading was seen on the purified fibrinogen-coated surface. White blood cells were present very early on surfaces precoated with vWF and partially purified fibrinogen, and were present prior to embolization on all surfaces. Major conclusions from this work indicate that, although fibrinogen and fibronectin promote thrombogenesis when adsorbed to a surface, vWF is even more active in promoting platelet deposition and in anchoring thrombi to the surface of biomaterials. Thus, differences in vWF adsorption to biomaterials may be a determinant of surface-induced thrombogenesis.

Adsorption↗