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Biomedical subjects

S C Choi

Publications and source records attributed to S C Choi.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cross-national comparisons of ageing mothers of adults with intellectual disabilities.

Ageing (55+ years) mothers of adults with intellectual disabilities in the Republic of Ireland, Northern Ireland and the United States were compared with respect to three general issues. Firstly, to what extent do the adults in these three countries differ in their level of reliance on their mothers? Secondly, do the mothers differ in the extent to which they have made plans for the future care of their son or daughter with intellectual disabilities? Thirdly, do the mothers differ in physical, social and psychological well-being? These cross-national comparisons were undertaken to examine the extent to which lifelong caregiving has either a common influence on mothers across national boundaries, or, alternatively, whether the cultural context exerts a unique influence on mothers in each country. Findings supported the latter explanation, even when background characteristics were statistically controlled.

Adult↗
PubMed1995

Coagulopathy with the use of hetastarch in the treatment of vasospasm.

The use of colloid agents to achieve hypervolemia in the prevention and treatment of postsubarachnoid hemorrhage (post-SAH) vasospasm is included in the standard of care at many institutions. Risk profiles are necessary to ensure appropriate use of these agents. In a series of 85 patients with recent aneurysmal SAH, 26 developed clinical symptoms of vasospasm. Fourteen of the 26 were treated with hetastarch for volume expansion while the other 12 received plasma protein fraction (PPF). Clinically significant bleeding pathologies were noted in six patients who received hetastarch as a continuous intravenous infusion. Hetastarch increased partial thromboplastin time from a mean of 23.9 seconds to a mean of 33.1 seconds (p < 0.001) in all patients who received infusions of this agent, while no effect was noted in the 12 patients who received PPF infusions. No other coagulation parameters were altered. This study shows an increase in coagulopathy with the use of hetastarch as compared with the use of PPF for the treatment of postaneurysmal vasospasm.

Blood Coagulation Disorders↗
PubMed1995

Effects of endoscopic variceal ligation in lower esophageal motor function: a prospective study.

OBJECTIVES: Endoscopic variceal ligation (EVL), a recently developed method for controlling active variceal bleeding and eradicating esophageal varices, has similar efficacy to endoscopic injection sclerotherapy (EIS) and is known to have a minimal risk of complications and fewer complications in the lower esophagus. However, since the site of EVL is chiefly done in the lower esophagus, we prospectively evaluated to investigate the effect of EVL on the lower esophageal motor function. METHODS: We evaluated the severity of esophageal varix with the endoscopy and the lower esophageal manometry in 27 patients who had no history of interventional therapy, for varices before EVL, 3 weeks and 6 months after the last EVL session. RESULTS: The EVL caused considerable diminution in the size of esophageal varix by a mean 8.2 (range 3-21) ligations in mean 1.7 (range 1-3) sessions. In most of the cases, the varices reappeared and enlarged when the procedure of EVL was stopped. There were two different types of changes (intermediate and late) in the lower esophageal motility. The intermediate post-EVL effects were the increase of peristaltic contraction amplitude and duration in the lower esophageal body after EVL. The late post-EVL effects were the prolongation of lower esophageal sphinctor (LES) relaxation duration and speedier peristaltic velocity in the lower esophageal body. CONCLUSIONS: We conclude from these findings that the intermediate post-EVL effect may be transient and the increase of peristaltic wave was due to diminution of esophageal varix.

Adult↗
PubMed1994

Sequential method of estimating the LD50 using a modified up-and-down rule.

In this paper, the original up-and-down method, modified up-and-down method, the Robbins-Monro method, and a fixed-sample Spearman-Kärber method are compared for the point estimator as well as the confidence interval of LD50. In particular, three different designs of the modified up-and-down approach based on the combination of experiments on one test space and reduced test space are investigated. The standard normal distribution and chi-square distribution are used as tolerance distributions. Simulation results indicate that the modified up-and-down method tends to be somewhat better than the original up-and-down method in terms of the mean squared error under normal tolerance distribution. In case of chi-square distribution, the modified method is shown to be substantially better when the test space is wide and the initial dose is further away from the LD50.

Lethal Dose 50↗
PubMed1994

Metabolic Pathways Leading to Mercury Methylation in Desulfovibrio desulfuricans LS.

The synthesis of methylmercury by Desulfovibrio desulfuricans LS was investigated on the basis of C incorporation from precursors and the measurement of relevant enzyme activities in cell extracts. The previously observed incorporation of C-3 from serine into methylmercury was confirmed by measurement of relatively high activities of serine hydroxymethyltransferase and other enzymes of this pathway. High rates of label incorporation into methylmercury from HCOO and HCO(3) prompted the assay of enzymes of the acetyl coenzyme A (CoA) synthase pathway. These enzymes were found to be present but at activity levels much lower than those reported for acetogens. Propyl iodide inhibited methylmercury and acetyl-CoA syntheses to similar extents, and methylmercury synthesis was found to compete with acetyl-CoA synthesis for methyl groups. On the basis of these findings, we propose that in methylmercury synthesis by D. desulfuricans LS the methyl group is transferred from CH(3)-tetrahydrofolate via methylcobalamin. The methyl group may originate from C-3 of serine or from formate via the acetyl-CoA synthase pathway. These pathways are not unique to D. desulfuricans LS, and thus the ability of this bacterium to methylate mercury is most likely associated with the substrate specificity of its enzymes.

Journal Article↗
PubMed1994

Enzymatic catalysis of mercury methylation by Desulfovibrio desulfuricans LS.

The recently defined role of methylcobalamin in Hg2+ methylation by Desulfovibrio desulfuricans LS enabled us to reexamine the question of whether the principal source of methylmercury is spontaneous transmethylation or an enzymatically catalyzed process. In cell extracts of D. desulfuricans LS, over 95% of the 57Co label was associated with macromolecules rather than with free cobalamin. Both gel filtration and electrophoresis of cell extracts identified a single corrinoid protein of 40 kDa in size. This finding, in combination with the previously reported light-reversible propyl iodide inhibition of the Hg2+ methylation process, led us to propose that this 40-kDa corrinoid protein is the in vivo methyl donor in D. desulfuricans LS. Under reducing conditions, cell extracts containing the corrinoid protein produced 14CH3Hg+ from Hg2+ and 5-14CH3-tetrahydrofolate with a maximum specific activity of 0.73 nmol min-1 mg of cell protein-1. The sequence of methyl transfer was from methyltetrahydrofolate to the corrinoid protein to Hg2+. The rate of methylation versus the Hg2+ concentration followed Michaelis-Menten kinetics, with an apparent Km of 0.87 mM HgCl2. The activity was oxygen sensitive, and Hg2+ methylation was optimal at 35 degrees C and pH 6.5. The observation of saturation kinetics and the 600-fold-higher rate of Hg2+ methylation (at pH 7.0) by cell extracts, compared with transmethylation by free methylcobalamin, proved that in vivo Hg2+ methylation is an enzymatically catalyzed process.

Bacterial Proteins↗
PubMed1994

Temporal profile of outcomes in severe head injury.

The authors present data describing the temporal progress of 786 severely head-injured patients from discharge to 12 months postinjury. Changes in outcome over time are characterized and the effects on these changes of patient age, Glasgow Coma Scale score, pupillary response, and type of injury are investigated. The feasibility of using these factors and the outcome at 3 months postinjury to predict the outcome at 6 months post-trauma is explored via logistic regression analysis. The data indicate that a significant proportion of patients improve continuously during the first 6 months after injury; outcome tends to stabilize thereafter, which suggests that the response at this time may be the appropriate end point for clinical trials in severe head injury. Dichotomized outcomes are predictable with approximately 94% accuracy at 6 months postinjury; therefore, missing outcomes may safely be replaced by the corresponding predicted outcomes. The findings also indicate striking improvement over time in patients who are in a vegetative state at discharge, suggesting that decisions regarding withdrawal of supportive care should be postponed until 6 months after injury in these patients.

Adolescent↗
PubMed1993

Traumatic brain tissue acidosis: experimental and clinical studies.

We have been focusing on potential metabolic derangement associated with severe head injury and a clinical trail directed toward treating brain tissue acidosis is currently underway. More specifically, we based this study on the hypothesis that following brain trauma brain tissue acidosis develops which may contribute to the prolongation of coma and neurologic deficit. Tromethamine (THAM), a safe and low toxicity agent which buffers in major part by causing a hypocapnic alkalosis, was selected for trial. Patients admitted with GCS < 8 were randomized into one of three arms: control: THAM plus hyperventilation; hyperventilation alone. Each regimen was maintained for 5 days post injury. Our analysis of 3 and 6 months Glasgow outcome score showed that prophylactic hyperventilation retards recovery, and the use of THAM overcomes the apparent deleterious effects of hyperventilation. One explanation is that the reduced ICP instability observed in THAM treated patients may account for this improvement. Is THAM effective in buffering traumatized brain tissue? What factors account for improvement in ICP stability? We addressed these questions in experimental studies utilizing MR spectroscopy to measure brain lactate production and tissue pH in fluid percussed anaesthetized cats. The protocol was designed to match our clinical trial, and brain injured animals were randomized into control, THAM, and hyperventilated groups. We observed that brain lactate production increased with trauma and remained above control at 8 hrs post injury. Lactate production in THAM treated animals was not elevated. Highest lactate production was associated with injured animals treated with sustained hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1993

A phase II study of moderate hypothermia in severe brain injury.

Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.

Adolescent↗
PubMed1993

Effect of continuous rotational therapy on intracranial pressure in the severely brain-injured patient.

OBJECTIVE: To determine the effect of continuous rotational therapy on the dynamics of intracranial pressure. DESIGN: A controlled, prospective evaluation of intracranial pressure during continuous rotation therapy. SETTING: Neuroscience intensive care unit in a university hospital. PATIENTS: A total of 58 severely brain-injured patients (Glasgow Coma Score of < or = 9) ranging in age from 14 to 81 yrs. INTERVENTIONS: All patients had intraventricular catheters placed to continuously monitor intracranial pressure and all patients were placed on continuous rotational therapy once stabilized. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure data were measured in each patient during nonrotation and these data were compared with intracranial pressure data during rotation, thus allowing each patient to serve as their own control. In addition, the intracranial pressure during rotation (40 degrees from center) was further analyzed to determine the effect of angulation on the intracranial pressure. Analysis of computer-recorded intracranial pressure data showed no significant difference in intracranial pressure measured during rotation and nonrotation over the first 5 days postinjury. Minimal differences in intracranial pressure (< 1 to 2 mm Hg) were noted in right/center/left positions. It was also determined that intracranial pressure increased up to 6.5 mm Hg (p = .12) in patients who presented with a unilateral lesion on admission computed tomography when they rotated to the side of the lesion. However, these fluctuations did not promote additional intracranial pressure management. CONCLUSIONS: We conclude that the systemic benefits known to be derived from the use of continuous rotation therapy in the severely head-injured patient can be sustained without any deleterious effects on the intracranial pressure.

Adult↗
PubMed1993

Cobalamin-mediated mercury methylation by Desulfovibrio desulfuricans LS.

The prominence of sulfate reducers in mercury biomethylation prompted the examination of the methyl carrier and mercury methylation activity of Desulfovibrio desulfuricans LS. There was a low degree of mercury tolerance and a high degree of methylation during fermentative growth; the opposite was true during sulfate reduction. During 2 days of fermentative growth, up to 37% of HgCl2 was methylated at 0.1 micrograms/ml, but only 1.5% was methylated at 10.0 micrograms/ml. Less than 1% of the added HgCl2 was methylated under sulfate-reducing conditions. D. desulfuricans LS radioimmunoassay results were positive for cobalamin. The addition of CoCl2 and benzimidazole to fermentative cultures increased methylation activity. From D. desulfuricans LS grown in the presence of (57)CoCl2, a corrinoid was extracted and purified. High-performance liquid chromatography analysis of the purified extract yielded a single peak with the retention time of cobalamin, and 97% of the (57)Co radioactivity was associated with this peak. Fast atom bombardment and UV and visible spectra of the isolated corrinoid matched those of cobalamin. When methylated with (14)CH3I, the isolated corrinoid methylated Hg(2+) with a 93.9% preservation of (14)C specific activity. We conclude that D. desulfuricans LS methylates mercury via cobalamin (vitamin B12). Under physiological conditions, the enzymatic catalysis of this reaction is likely.

Corrinoids↗
PubMed1993

Enhanced oxygenation in vivo by allosteric inhibitors of hemoglobin saturation.

The in vivo effects on hemoglobin (Hb)-O2 affinity and tissue PO2 were investigated after intraperitoneal administration of 2-[4-(((dichloroanilino)-carbonyl)methyl)phenoxyl]-2-methyl propionic acid (RSR4; 150 mg/kg) or its 3,5-dimethyl derivative (RSR13; 300 mg/kg) in C3Hf/Sed mice. The Hb-O2 dissociation curve was plotted from tail vein blood samples using an O2 dissociation analyzer before and up to 160 min after compound administration. Twenty to 40 min after injection, the PO2 at 50% saturation of hemoglobin (Hb P50) increased by a mean of 25% (range 18-31%) after RSR4 and 53% (range 36-76%) after RSR13. Tissue PO2 was continuously measured using an O2 microelectrode in thigh muscle before and up to 40 min after RSR4 or RSR13 injection. Twenty to 40 min after administration, tissue PO2 increased by a mean of 78% (range 30-127%) after RSR4 and 66% (range 39-97%) after RSR13 administration in anesthetized mice. No change in tissue PO2 was seen in anesthetized controls.

Aniline Compounds↗
PubMed1993

Relationship between Glasgow Outcome Scale and neuropsychological measures after brain injury.

The present study was conducted to further our understanding of the relationship between performance on neuropsychological tests and functional status after head injury and to provide information on the relative usefulness of neuropsychological tests as outcome measures in clinical trials of brain injury. We sought to select the fewest number of 19 neuropsychological tests administered to 110 patients that, in combination, were most closely related to outcome (as measured by the Glasgow Outcome Scale (GOS) and to the remaining neuropsychological measures. The relationship of memory and intellectual deficits to functional status was also considered. To address these questions, we analyzed 19 neuropsychological measures and GOS scores of 110 severely brain injured patients from the Traumatic Coma Data Bank. Of 19 neuropsychological measures compared with GOS at 3 and 6 months, four tests (Controlled Oral Word Association, Grooved Pegboard, Trailmaking Part B, and Rey-Osterrieth Complex Figure Delayed Recall) provided the closest relationship to GOS and to the remaining 15 tests. Similar analyses were performed on 30 moderately injured patients to test the generality of our findings across different levels of patient severity. The same four tests were found to be highly predictive of GOS. Grooved Pegboard, a test of fine motor coordination, accounted for 80% of the variation in GOS. Fifteen percent of 116 patients with severe brain injury could not complete a neuropsychological battery and 39% were excluded because of previous brain injury or known substance abuse.

Adolescent↗
PubMed1993

Improving the outcome of severe head injury with the oxygen radical scavenger polyethylene glycol-conjugated superoxide dismutase: a phase II trial.

Formation of the oxygen radical superoxide anion is one of the final events of several metabolic pathways in the cascade that leads to delayed neuronal death after traumatic or ischemic brain injury. In the laboratory, scavenging of the superoxide anion with native superoxide dismutase (SOD) or polyethylene glycol (PEG)-conjugated SOD (PEG-SOD) has been shown to be beneficial in several types of traumatic and ischemic injury. Accordingly, PEG-SOD was utilized in a randomized controlled Phase II trial to evaluate its safety and efficacy in severely head-injured patients with a Glasgow Coma Scale score of 8 or less. At two institutions, 104 patients were randomly assigned to receive either placebo or PEG-SOD (2000, 5000, or 10,000 U/kg) intravenously as a bolus, an average of 4 hours after injury. Prognostic factors were evenly distributed in the four groups, except for mean age which was significantly higher in the group receiving 10,000 U/kg than in the placebo group (mean age 34 years vs. 25 years). No complications attributed to the study medication were noted. The average intracranial pressure (ICP) was similar in the four groups, but the percentage of time during which ICP was above 20 mm Hg was less in the groups receiving 5000 or 10,000 U/kg of PEG-SOD. Patients in the group receiving 10,000 U/kg also required less mannitol for ICP control than the placebo group. Outcome was assessed using the Glasgow Outcome Scale at 3 and 6 months postinjury in 91 and 93 patients, respectively, by blinded observers not involved in the clinical management of the patients. At 3 months, 44% of patients in the placebo group were vegetative or had died, while only 20% of patients in the group receiving 10,000 U/kg of PEG-SOD were in these outcome categories (p < 0.03, multiple logistic regression test); at 6 months, these figures were 36% and 21%, respectively (p = 0.04). Differences in outcome between the placebo group and either of the other two dosage groups were not statistically significant. It is concluded that PEG-SOD was generally well tolerated and appears promising in improving outcome after severe head injury. A larger, multicenter, Phase III trial, using a higher dose (20,000 U/kg) compared to placebo and to 10,000 U/kg of PEG-SOD is planned.

Adult↗
PubMed1993

Effect of neonatal capsaicin treatment on neurogenic pulmonary edema from fluid-percussion brain injury in the adult rat.

The frequent occurrence of acute death from pulmonary failure in experimental head injury studies on Sprague-Dawley rats prompted an investigation into the manner in which acute neurogenic pulmonary edema develops in these animals as a result of an applied fluid pressure pulse to the cerebral hemispheres. Studies were performed in adult animals using histamine H1 and H2 blocking agents, or in adult animals treated as neonates with capsaicin to destroy unmyelinated C-fibers. Recordings were made of either the pulmonary arterial or the right ventricular pressure, and the left atrial and femoral arterial pressures before, during, and after injury to provide a record of the hemodynamic response throughout the development of neurogenic pulmonary edema. Head injury triggered the almost immediate development of pressure transients with and without neurogenic pulmonary edema. All rats, regardless of treatment, reacted with nearly identical systemic arterial pressure responses; however, the pulmonary responses followed a time course that was independent of systemic arterial pressure changes. Acute neurogenic pulmonary edema was always associated with a substantial increase in pulmonary arterial and left atrial pressures; conversely, pressure increases of similar magnitude were not always associated with edema. Histamine H1 and H2 blockers significantly reduced the pulmonary pressure surges only in rats free of neurogenic pulmonary edema. All capsaicin-treated rats showed suppressed pulmonary pressure responses, normal lung water content, elevated lung surface tension, and significantly reduced levels of immunoreactive substance P in the spinal cord and vagus nerve. While the pressures cannot clarify how edema influences the observed hemodynamics, they do not support the view that edema is the direct consequence of pulmonary hypertension. It is proposed that neurogenic pulmonary edema is a functional disturbance provoked by adverse stimuli from outside the lungs and that in the rat the primary afferent fiber is essential to the production of this entity.

Animals↗
PubMed1992

Outcome measures for clinical trials involving traumatically brain-injured patients: report of a conference.

A conference was held in Houston, Texas, on October 8-9, 1991, to develop recommendations for outcome measures for clinical trials in traumatic brain injury. Participants, all experts in this area, discussed and agreed on treatments for patients with severe brain injury (Glasgow Coma Score [GCS] < or = 8) and moderate brain injury (GCS, 9-12). A parallel trial design was recommended rather than a factorial, sequential, or crossover design. It was agreed that stratifying randomization based on motor score alone or on a combination of motor score and age would result in increased power. Acute stage measurements, such as cerebral blood flow, cerebrospinal fluid biochemistry, and evoked potentials, were recommended only when they satisfied a specific hypothesis. Functional outcome measures were recommended as the primary outcome measure for severe brain injury (GCS, 3-8). Either the Glasgow Outcome Scale or Disability Rating Scale, measured at 6 months after injury, were recommended as the primary outcome measure for severe brain injury (GCS, < or = 8). For patients with moderately severe brain injury (GCS, 9-12), the Disability Rating Scale at 3 months after injury was recommended as the primary outcome measure. The Neurobehavioral Rating Scale appears to be a satisfactory instrument for measuring behavioral changes. Specific neuropsychological measures were recommended as supplementary outcome measures for both severe and moderate brain injury, consistent with a 1.5-hour period available for testing.

Adolescent↗
PubMed1992

Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography.

The role of cerebral ischemia in the pathophysiology of traumatic brain injury is unclear. Cerebral blood flow (CBF) measurements with 133Xe have thus far revealed ischemia in a substantial number of patients only when performed between 4 and 12 hours postinjury. But these studies cannot be performed sooner after injury, they cannot be done in patients with intracranial hematomas still in place, and they cannot detect focal ischemia. Therefore, the authors performed CBF measurements in 35 comatose head-injured patients using stable xenon-enhanced computerized tomography (CT), simultaneously with the initial CT scan (at a mean (+/- standard error of the mean) interval of 3.1 +/- 2.1 hours after injury). Seven patients with diffuse cerebral swelling had significantly lower flows in all brain regions measured as compared to patients without swelling or with focal contusions; in four of the seven, cerebral ischemia (CBF less than or equal to 18 ml/100 gm.min-1) was present. Acute intracranial hematomas were associated with decreased CBF and regional ischemia in the ipsilateral hemisphere, but did not disproportionately impair brain-stem blood flow. Overall, global or regional ischemia was found in 11 patients (31.4%). There was no correlation between the presence of hypoxia or hypertension before resuscitation and the occurrence of ischemia, neither could ischemia be attributed to low pCO2. Ischemia was significantly associated with early mortality (p less than 0.02), whereas normal or high CBF values were not predictive of favorable short-term outcome. These data support the hypothesis that ischemia is an important secondary injury mechanism after traumatic brain injury, and that trauma may share pathophysiological mechanisms with stroke in a large number of cases; this may have important implications for the use of hyperventilation and antihypertensive drugs in the acute management of severely head-injured patients, and may lead to testing of drugs that are effective or have shown promise in the treatment of ischemic stroke.

Adolescent↗