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S C Choi

Publications and source records attributed to S C Choi.

At least 19 recordsLinked to original sources

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

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

Prediction tree for severely head-injured patients.

Prediction tree techniques are employed in the analysis of data from 555 patients admitted to the Medical College of Virginia hospitals with severe head injuries. Twenty-three prognostic indicators are examined to predict the distribution of 12-month outcomes among the five Glasgow Outcome Scale categories. A tree diagram, illustrating the prognostic pattern, provides critical threshold levels that split the patients into subgroups with varying degrees of risk. It is a visually useful way to look at the prognosis of head-injured patients. In previous analyses addressing this prediction problem, the same set of prognostic factors (age, motor score, and pupillary response) was used for all patients. These approaches might be considered inflexible because more informative prediction may be achieved by somewhat different combinations of factors for different patients. Tree analysis reveals that the pattern of important prognostic factors differs among various patient subgroups, although the three previously mentioned factors are still of primary importance. For example, it is noted that information concerning intracerebral lesions is useful in predicting outcome for certain patients. The overall predictive accuracy of the tree technique for these data is 77.7%, which is somewhat higher than that obtained via standard prediction methods. The predictive accuracy is highest among patients who have a good recovery or die; it is lower for patients having intermediate outcomes.

Adult

Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia.

Although experimental and pathological studies suggest an important role for ischemia in the majority of fatal cases of traumatic brain injury, ischemia has been a rare finding in most clinical studies of cerebral blood flow (CBF) in head-injured patients. The hypothesis of the present study was that cerebral ischemia occurs in the first few hours after injury, but that CBF measurements have not been performed early enough. Early measurements of CBF (by the 133Xe intravenous method) and arteriovenous oxygen difference (AVDO2) were obtained in 186 adult head-injured patients with a Glasgow Coma Scale score of 8 or less, and were correlated with neurological status and outcome. During the first 6 hours after injury, CBF was low (22.5 +/- 5.2 ml/100 gm/min) but increased significantly during the first 24 hours. The AVDO2 followed the opposite course; the decline of AVDO2 was most profound in patients with low motor scores, suggesting relative hyperemia after 24 hours. A significant correlation between motor score and CBF was found in the first 8 hours after injury (Spearman coefficient = 0.69, p less than 0.001), but as early as 12 hours postinjury this correlation was lost. A similar pattern was found for the relationship between CBF and outcome. Cerebral blood flow below the threshold for infarction (CBF less than or equal to 18 ml/100 gm/min) was found in one-third of the studies obtained within 6 hours, the incidence rapidly decreasing thereafter. A low CBF after 24 hours was not generally associated with a high AVDO2, and was probably a reflection of low oxidative metabolism rather than frank ischemia. In 24 patients, a CBF of 18 ml/100 gm/min or less was found at some point after injury; the mortality rate was significantly higher in this subgroup, and survivors did worse. In some cases, ischemia was successfully treated by reducing hyperventilation or inducing arterial hypertension. These results support the above hypothesis, and suggest that early ischemia after traumatic brain injury may be an important factor determining neurological outcome. Moreover, these data indicate that early hyperventilation or lowering of blood pressure to prevent brain edema may be harmful.

Adolescent

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial.

There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Vitamin B12S-promoted model rearrangement of methylmalonate to succinate is not a free radical reaction.

To probe for free radical intermediates in the model methylmalonate to succinate rearrangements promoted by vitamin B12s, a model series with a pentenyl side chain radical trap has been devised. The control free radical, generated by tri-n-butyltin hydride treatment of bromomethyl-pentenylmalonate thioester, undergoes rapid cyclization to the six-membered ring, and, as anticipated, no succinate rearrangement product is detected. By contrast when the bromide is treated with vitamin B12s, little cyclized product is observed; the major product is the pentenyl succinate. This result demonstrates that the latter rearrangement does not follow a free radical pathway.

Chemical Phenomena

[Panoramic image of the hard palate and the nasal floor].

The author investigated the origin of two linear radiopaque images superimposed upon the lower part of the maxillary antra and nasal cavity. The obtained results were as follows: 1. The upper blurred image was not the ghost image of the lower sharp image. 2. The upper image was not formed by the horizontal plate of palatine bone and the lower image was not formed by the palatal process of maxilla. 3. The upper image and lower image seemed to be formed by the junction of the nasal septum to the hard palate and by the junction of the maxillary antrum and the hard palate respectively. But there were some unidentified structures which formed these two images.

Humans

Interval estimation of the LD50 based on an up-and-down experiment.

It is well known that an up-and-down method can be more efficient than fixed-sample methods in estimating the LD50 of a quantal response curve. A problem that has not been addressed by many is that of obtaining a confidence interval for the LD50 from the up-and-down method. Dixon and Mood (1948, Journal of the American Statistical Association 43, 109-126) proposed a confidence interval using a maximum likelihood approach, but not much is known about its properties. In this paper, a new confidence interval for the LD50 based on turning points is obtained, which uses the concept of phi-mixing. Simulation results indicate that the coverage probabilities of both methods tend to be less than the nominal level unless the sample size is large. Even so, when the tolerance distribution is normal, the proposed confidence interval is found to be superior to Dixon's interval in terms of the coverage, the width, and stability. The advantages of the method do not appear to hold in the presence of nonnormal tolerance distribution.

Animals

Conditions for pharmacologic evaluation in the gerbil model of forebrain ischemia.

We looked at FiO2, choice of anesthetic, nutritional status, and body temperature in a gerbil model of forebrain ischemia to determine their effect on data interpretation, ischemic outcome, and extent of pharmacologic protection. We subjected 484 gerbils to 5 minutes of forebrain ischemia under different experimental conditions. The gerbils were anesthetized with 3% halothane and inspired 21% O2, 37% O2 and 60% N2O, or 97% O2. Six groups of gerbils pretreated with 200 mg/kg phenytoin or 2 ml/kg polyethylene glycol (vehicle) underwent ischemia in the fasted or fed state. Three groups of gerbils receiving no pretreatment underwent ischemia with rectal temperatures of 32-33 degrees C, 34-35 degrees C, or 37 degrees C. We counted intact neurons in the CA1 hippocampal sector in brains fixed on Day 7 after ischemia. t tests of square-root-transformed cell counts were used to assess the effect of hypothermia, and analysis of variance of the transformed data was used to test for the effects of phenytoin, FiO2, and nutritional status. Phenytoin pretreatment provided significant protection from CA1 neuron loss in all groups tested (p less than 0.001), but the degree of protection varied from 20% to 44%. In spite of significantly higher serum glucose concentrations in fed than in fasted gerbils (173 and 118 mg/dl, respectively), we found no significant effect of nutritional status upon neuron loss in phenytoin- or vehicle-pretreated gerbils. An FiO2 of 21% significantly decreased the number of viable neurons in both vehicle- and phenytoin-pretreated groups (p less than 0.03), despite the lack of an effect of hypoxemia on arterial blood gases.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia

Cerebral blood flow and metabolism in severely head-injured children. Part 1: Relationship with GCS score, outcome, ICP, and PVI.

The literature suggests that in children with severe head injury, cerebral hyperemia is common and related to high intracranial pressure (ICP). However, there are very few data on cerebral blood flow (CBF) after severe head injury in children. This paper presents 72 measurements of cerebral blood flow ("CBF15"), using the 133Xe inhalation method, with multiple detectors over both hemispheres in 32 children aged 3 to 18 years (mean 13.6 years) with severe closed head injury (average Glasgow Coma Scale (GCS) score 5.4). In 25 of the children, these were combined with measurements of arteriojugular venous oxygen difference (AVDO2) and of cerebral metabolic rate of oxygen (CMRO2). In 30 patients, the first measurement was taken approximately 12 hours postinjury. In 18 patients, an indication of brain stiffness was obtained by withdrawal and injection of ventricular cerebrospinal fluid and calculation of the pressure-volume index (PVI) of Marmarou. The CBF and CMRO2 data were correlated with the GCS score, outcome, ICP, and PVI. Early after injury, CBF tended to be lower with lower GCS scores, but this was not statistically significant. This trend was reversed 24 hours postinjury, as significantly more hyperemic values were recorded the lower the GCS score, with the exception of the most severely injured patients (GCS score 3). In contrast, mean CMRO2 correlated positively with the GCS score and outcome throughout the course, but large standard deviations preclude making predictions based on CMRO2 measurements in individual patients. Early after injury, there was mild uncoupling between CBF and CMRO2 (CBF above metabolic demands, low AVDO2) and, after 24 hours, flow and metabolism were completely uncoupled with an extremely low AVDO2. Consistently reduced flow as found in only four patients; 28 patients (88%) showed hyperemia at some point in their course. This very high percentage of patients with hyperemia, combined with the lowest values of AVDO2 found in the literature, indicates that hyperemia or luxury perfusion is more prevalent in this group of patients. The three patients with consistently the highest CBF had consistently the lowest PVI: thus, the patients with the most severe hyperemia also had the stiffest brains. Nevertheless, and in contrast to previous reports, no correlation could be established between the course of ICP or PVI and the occurrence of hyperemia, nor was there a correlation between the levels of CBF and ICP at the time of the measurements. The authors argue that this lack of correlation is due to: 1) a definition of hyperemia that is too generous, and 2) the lack of a systematic relationship between CBF and cerebral blood volume

Adolescent

Combined effect of respirator-induced ventilation and superoxide dismutase in experimental brain injury.

The function-specific enzyme superoxide dismutase (SOD) was tested for its protective effect in severe experimental fluid-percussion brain injury (4.45 +/- 0.10 atm) in 30 of 60 randomly selected male Sprague-Dawley rats. A respirator was used only in the event of need. The number of animals with permanent resumption of spontaneous breathing (Type I respiratory response) remained essentially the same in each group. However, when Type II apnea (cannot maintain recovery) and Type III apnea (never recovers from the initial apnea) were terminated with a respirator, all rats with Type II responses from each group were successfully converted to a state of sustained spontaneous breathing. In contrast, only five (41.7%) of the 12 rats with Type III response were salvaged in the control group while five (83.3%) of six Type III rats in the SOD-treated group were saved. The results reveal the nature of the therapeutic effectiveness of superoxide radical scavengers in the overall outcome of head injury in this animal model. While SOD alone did not increase the number of spontaneous survivors, the drug shifted a number of animals from the critically injured rats with Type III respiratory response to the less critical Type II condition. Whereas induced respiration as the sole therapy in the control group lowered the mortality rate to 23.3%, respiratory assistance together with SOD treatment reduced the "mortality" to a single animal with Type III apnea (3.3%) which was alive but still required the respirator after 2 hours (p less than 0.001). The results show that respiratory assistance alone accounted for a 33% decrease in mortality rate and that SOD, given in addition to induced ventilation, further decreased mortality by 20%. Since SOD enzymes are reactively specific for superoxide, the increased survival rate of the brain-injured rat must have been due either to preventing or to minimizing pathophysiological changes, probably in the brain stem, caused by oxygen free radicals.

Animals

Monitoring clinical trials based on predictive probability of significance.

At a given point in a clinical trial, investigators may ask the question: "What is the likelihood of a significant result if the trial were continued?" One possible answer to this question is to examine a predictive probability of the significant difference with further patient accrual. [See, for example, Choi, Smith, and Becker (1985, Controlled Clinical Trials 6, 280-288).] This paper proposes and investigates the approach in trials for comparing the means of two normal populations. Two methods for calculating the predictive probability are examined. The results indicate that the predictive probability can be a useful conservative measure in monitoring trials.

Bayes Theorem

Comparing incomplete paired binomial data under non-random mechanisms.

In many paired experiments designed to compare two treatments, various mechanisms can lead to the data being incomplete. Such mechanisms may be of a non-random nature and may depend on the treatment or the outcome. This paper considers several methods for testing the equality of two correlated binomial proportions when the incompleteness is caused by non-random mechanisms. Several simple procedures are justified in certain cases. The tests based on all available data are more efficient compared to those utilizing only portions of the data. McNemar's test based only on the complete paired observations and the likelihood test are the most robust, although no efficient test exists when the mechanisms are not independent.

Craniocerebral Trauma

Enhanced specificity of prognosis in severe head injury.

Data from 523 patients admitted to the Medical College of Virginia with severe head injury and known 6-month outcomes were analyzed in order to determine the optimal combination of early-available prognostic factors. Twenty-one prognostic indicators noted in the emergency room at admission were used to predict outcomes into four categories: good, moderately disabled, severely disabled, or vegetative/dead. A combination of the patient's age (in years), the best motor response (graded in the usual six-point scale), and pupillary response (in both eyes) was found to be the most accurate indicator. The model correctly predicted outcome into one of the four outcome categories in 78% of cases ("specifically accurate predictions"). If predictions into an outcome category adjacent to the actual outcome were accepted, this model was accurate in 90% of cases ("grossly accurate predictions"). A set of three simple graphs based on this model can be used for rapid early estimation of probable outcome in a severely head-injured patient at admission.

Adult

The urinary diary in evaluation of incontinent women: a test-retest analysis.

This study investigated the use of a one-week urinary diary in the evaluation of incontinent women. The sample consisted of 50 community-dwelling women, ages 55 years and older, ambulatory, and mentally intact, who were volunteers in a clinical trial on behavioral management for urinary incontinence. All subjects kept a urinary diary for two consecutive weeks. An analysis of the immediate (one-week) test-retest variability and correlations on weekly diurnal micturition frequency, nocturnal micturition frequency, and urinary incontinent episodes were performed in subjects with sphincteric incompetence alone (N = 34) and in those with detrusor instability with or without concomitant sphincteric incompetence (N = 16). In addition, information obtained on history was compared with that obtained from the diary. Diurnal micturition frequency, nocturnal micturition frequency, and number of incontinent episodes were highly reproducible and did not differ by urodynamic diagnosis. Test-retest correlations were highest with diurnal micturition frequency and incontinent episodes. Lower correlations were observed with nocturnal micturition frequency, with a significant difference observed between diagnostic groups. Although modest, significant relationships between data collected by history and diary were observed in the overall sample, but there were significant differences between diagnostic groups. The results indicate that a one-week diary is a reliable method for assessing the frequency of voluntary micturitions and involuntary episodes of urine loss.

Aged

Xenon/computed tomography cerebral blood flow measurements. Methods and accuracy.

We performed a series of five baboon experiments to compare cerebral blood flow measured with an improved stable xenon/CT method and the radiolabelled microsphere technique at a PaCO2 of 40 mm Hg. The xenon/CT method was implemented by fitting the arterial xenon uptake with a double exponential function, by measuring the oxygen and carbon dioxide concentrations continuously during each breath and by taking into account the lung-to-brain transit time of xenon. The time of xenon inhalation was extended to 30 minutes to obtain more reliable estimates of CBF in white matter regions. The results indicate an overall correlation coefficient of 0.92 between the two methods and good numeric agreement.

Animals

Outcome after severe head injury. Relationship to mass lesions, diffuse injury, and ICP course in pediatric and adult patients.

A consecutive series of 330 severely head-injured patients was studied prospectively. All of the patients were treated with the same protocols by the same physicians and staff in the same intensive care unit. All of the patients had intracranial pressure (ICP) monitoring. Of the 330 patients, 100 were in the pediatric age group (0 to 19 years of age) and 230 were in the adult group (20 to 80 years of age). Statistical analyses were performed with regard to outcome, Glasgow Coma Scale (GCS) score, ICP course, and incidence of surgical lesions. The average emergency room GCS score as well as the 24-hour GCS score for each group was the same. The percentage of patients having ICP that was normal, increased but reducible, and increased but not reducible in each group was the same. The pediatric patients had a significantly higher percentage of good outcomes (43%) than the adult patients (28%) (p less than 0.01). They also had a significantly lower mortality rate (24%) than the adult patients (45%) (p less than 0.01). At 1 year following injury, 55% of pediatric patients had a good outcome compared to 21% of adults (p less than 0.001); this trend was evident at 3 months, with the same p value. Pediatric patients with normal ICP had a higher percentage of good outcomes (70%) than the adult patients with normal ICP (48%) (p less than 0.05). There was no significant difference in outcome in pediatric and adult patients with mass lesions or with increased ICP, regardless of whether or not the pressure was reducible. There was a much higher incidence of surgical mass lesions in adult patients (46%) than in pediatric patients (24%) (p less than 0.001).

Adolescent