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Biomedical subjects

W E Wilkinson

Publications and source records attributed to W E Wilkinson.

At least 37 records · Page 2Linked to original sources

Magnetic resonance imaging of the corpus callosum: predictors of size in normal adults.

Eighty normal adults were studied with MRI to investigate the relationship between regional morphology of the corpus callosum and characteristics such as age, gender, education, and cranial size. The variability coefficient was 20% in total callosal area and from 19% to 40% in regional callosal area. Increasing age and smaller cranial area were both associated with smaller total and regional callosal areas; there were no effects of gender and education. The relative effects of age and cranial size varied across regions and were most prominent for anterior subdivisions. However, age and cranial size together explained less than half the variance in regional callosal size. Further study is needed to identify additional correlates of regional callosal anatomy.

Adult↗

Discrimination between stages of Alzheimer's disease with subsets of Mini-Mental State Examination items. An analysis of Consortium to Establish a Registry for Alzheimer's Disease data.

OBJECTIVE: To identify minimal sets of Mini-Mental State Examination (MMSE) items that can distinguish normal control subjects from patients with mild Alzheimer's disease (AD), patients with mild from those with moderate AD, and those with moderate from those with severe AD. DESIGN: Two randomly selected equivalent half samples. Results of logistic regression analysis from data from the first half of the sample were confirmed by receiver operating characteristic curves on the second half. SETTING: Memory disorders clinics at major medical centers in the United States affiliated with the Consortium to establish a Registry for Alzheimer's Disease (CERAD). PARTICIPANTS: White, normal control subjects (n = 412) and patients with AD (n = 621) who met CERAD criteria; nonwhite subjects (n = 165) and persons with missing data (n = 27) were excluded. MAIN OUTCOME MEASURES: Three four-item sets of MMSE items that discriminate, respectively, (1) normal controls from patients with mild AD, (2) patients with mild from those with moderate AD, and (3) patients with moderate from those with severe AD. RESULTS: The MMSE items discriminating normal controls from patients with mild AD were day, date, recall of apple, and recall of penny; those discriminating patients with mild from those with moderate AD were month, city, spelling world backward, and county, and those discriminating patients with moderate from those with severe AD were floor of building, repeating the word table, naming watch, and folding paper in half. Performance on the first two four-item sets was comparable with that of the full MMSE; the third set distinguished patients with moderate from those with severe AD better than chance. CONCLUSIONS: A minimum set of MMSE items can effectively discriminate normal controls from patients with mild AD and between successive levels of severity of AD. Data apply only to white patients with AD. Performance in minorities, more heterogeneous groups, or normal subjects with questionable cognitive status has not been assessed.

Aged↗

Evaluation of outpatients experiencing implantable cardioverter defibrillator shocks associated with minimal symptoms.

Patients receiving minimally symptomatic shocks from their implantable cardioverter defibrillators were studied prospectively using transtelephonic ECG loop monitoring. The time course to the first subsequent shock was evaluated. Twenty-nine consecutive patients who received a shock preceded by mild palpitations or no symptoms were given a transtelephonic ECG loop monitor and instructed to activate the monitor if a subsequent shock occurred. Kaplan-Meier analysis was used to quantitate the time to first shock during the study period. The point estimate +/- standard error of patients receiving a shock during the study period was 31% +/- 9% at 30 days, 41% +/- 9% at 60 days, and 60% +/- 9% at 120 days. The ECG was successfully transmitted in 7 of 13 patients who had shocks in the 60-day monitoring period, and demonstrated inappropriate shocks in 6 of 7. Determination of the cause of shock led to a change in subsequent management in all 7 patients. We conclude that the incidence of inappropriate shocks may be higher than estimated previously in patients with minimal symptoms prior to the shock. There are thousands of patients with implantable cardioverter defibrillators that have no storage function for treated tachycardias; transtelephonic ECG loop monitoring can determine the cause of implantable cardioverter defibrillator discharge in these patients, and the diagnosis is invaluable in their management.

Adolescent↗

Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia.

BACKGROUND: Paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are recognized clinically when patients seek treatment for symptoms due to recurrent arrhythmias; atrial fibrillation also increases the risk of stroke. The frequency with which asymptomatic arrhythmias occur in patients with these arrhythmias is unknown. METHODS AND RESULTS: Twenty-two patients with paroxysmal atrial fibrillation (n = 8) or paroxysmal supraventricular tachycardia (n = 14) were studied for 29 days with two different ambulatory ECG-monitoring techniques to measure the relative frequency of asymptomatic and symptomatic arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, beta-blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events (defined as lasting at least 30 seconds) were documented using continuous ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days; symptomatic arrhythmia events were documented using transtelephonic ECG monitoring for all 29 days of the study. In the group of patients with paroxysmal atrial fibrillation, asymptomatic arrhythmia events occurred significantly more frequently than symptomatic arrhythmia events; the mean rates, expressed as events/100 d/patient (95% confidence interval), were 62.5 (40.4, 87.3) and 5.2 (2.7, 9.0) (P < .01); the ratio of the mean rates was 12.1 (5.8, 26.4). In contrast, in the group of patients with paroxysmal supraventricular tachycardia, asymptomatic arrhythmia events were significantly less frequent than symptomatic arrhythmia events; the mean rates were 0.0 (0.0, 5.3) and 7.4 (5.0, 10.6) (P = .02). The ratio of the mean rates was 0.0 (0.0, 0.8). CONCLUSIONS: In a group of patients with paroxysmal atrial fibrillation, sustained asymptomatic atrial fibrillation occurs far more frequently than symptomatic atrial fibrillation. However, it is not known whether asymptomatic atrial fibrillation is a potential risk factor for stroke even when patients are not having symptomatic arrhythmias.

Atrial Fibrillation↗

The dexamethasone suppression test and quantitative cerebral anatomy in depression.

To determine whether structural brain abnormalities in patients with depression are related to cortisol state, we examined the relationship between the dexamethasone suppression test (DST) and brain magnetic resonance imaging (MRI) in 40 inpatients with severe depression referred for electroconvulsive therapy (ECT). Prior to ECT, 27 (68%) of the patients exhibited nonsuppression on the DST. Frontal lobe volume was negatively correlated with peak post-dexamethasone cortisone (r = -0.37) and was 13% smaller in DST nonsuppressors than suppressors; these findings were no longer significant after adjustments for age, gender, and cranial size. Lateral and third ventricular volumes were also correlated with peak postdexamethasone cortisol (r = 0.34 and 0.33, respectively), but not after adjustments for age, gender, and cranial size. Subcortical hyperintensity was associated with peak postdexamethasone cortisol and was more common in DST nonsuppressors than suppressors. Again these findings were no longer significant after adjustments for age. Finally, longitudinal DST and brain MRI studies in 11 of these patients revealed no changes in regional brain volumes nor in postdexamethasone cortisol up to six months after ECT. However, within individual patients, postdexamethasone cortisol was positively (and significantly) correlated with frontal lobe volume.

Adult↗

Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study.

Magnetic resonance imaging was used to examine cerebral anatomy in 48 inpatients with severe depression who were referred for electroconvulsive therapy and in 76 normal control subjects. The magnetic resonance imaging measures included determinations of regional cerebral volumes and ratings of the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. The mean total frontal lobe volume was found to be 7% smaller in the inpatients with severe depression (235.88 mL) than in the normal control subjects (254.32 mL)--a difference that was statistically significant even after adjusting for the effects of age, sex, education, and intracranial size. No group differences were observed in the volumes of the cerebral hemispheres, the temporal lobes, or the amygdala-hippocampal complex, nor in the frequency of cortical atrophy. Neither did the groups differ with respect to the total volumes of the lateral and third ventricles, nor in the frequency of lateral ventricular enlargement. Patients with depression had a significantly higher frequency of subcortical hyperintensity in the periventricular white matter, with an odds ratio of 5.32.

Adult↗

Spontaneous occurrence of symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia in untreated patients.

BACKGROUND: Ambulatory outpatients (n = 150) with a history of paroxysmal supraventricular arrhythmia were studied to establish the characteristics of the first recurrence of symptomatic tachycardia (time to first recurrence, heart rate during tachycardia, and observed rhythm that was regular versus irregular) when no antiarrhythmic drug was being taken. Baseline variables were examined to assess their impact on time to first recurrence: index arrhythmia (paroxysmal atrial fibrillation [n = 37] versus paroxysmal supraventricular tachycardia [n = 113]), age (mean +/- SD, 43.3 +/- 16.1 years), female sex (n = 71), or presence of other heart or lung disease (n = 53). METHODS AND RESULTS: Transtelephonic monitoring of the ECG was used to document the rhythm during recurrences of symptomatic tachycardia. Time to first recurrence of symptomatic tachycardia and heart rate during tachycardia were measured, the observed rhythm was classified as irregular (consistent with paroxysmal atrial fibrillation) or regular (consistent with paroxysmal supraventricular tachycardia), and the hour of recurrence was recorded. Advancing age was significantly associated with a decreasing time to first recurrence (p < 0.001); the estimated increase in the hazard function was 25% with each 10 years of advancing age. After the effect of age was adjusted for, neither the classification of arrhythmia (p > 0.2), presence of other heart or lung disease (p > 0.8), nor sex (p > 0.9) was significantly associated with time to first recurrence. Among patients with paroxysmal supraventricular tachycardia, 6.5% had atrial fibrillation recorded at the next symptomatic arrhythmia; among patients with paroxysmal atrial fibrillation, 11.8% had a regular tachycardia recorded at the next symptomatic arrhythmia. There was a circadian pattern to the hour of occurrence of paroxysmal supraventricular tachycardia but not paroxysmal atrial fibrillation. CONCLUSIONS: Age is more important than other clinical variables, including the ECG classification of a paroxysmal supraventricular arrhythmia in predicting the occurrence of symptomatic arrhythmias. Arrhythmias documented by ECG during symptoms are often different from the arrhythmia documented at the time of referral, which may confound interpretation of antiarrhythmic drug effects.

Adult↗

Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics.

Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.

Administration, Oral↗

Treatment of paroxysmal supraventricular tachycardia with oral diltiazem.

Symptomatic paroxysmal supraventricular tachycardia is a troubling arrhythmia for many patients. To test the efficacy of oral diltiazem to reduce symptomatic recurrences of paroxysmal supraventricular tachycardia, we enrolled 17 patients in a double-blind, placebo-controlled crossover study. Sixteen of 17 patients completed a dose-ranging phase and were entered into the randomized phase. Although the time to first recurrence of tachycardia was slightly longer when patients took diltiazem, the difference was not significant (p = 0.15). The hazard ratio of the time to first recurrence on placebo compared with oral diltiazem was 2.7 (95% confidence interval, 0.8 to 9.1). Of the patients who had a recurrence of tachycardia in both treatment periods, the median reduction in heart rate in patients receiving diltiazem was 20 beats/min. (p less than 0.01; 95% confidence interval, 6 to 42).

Administration, Oral↗

Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging.

Seventy-six healthy adults underwent magnetic resonance imaging (1.5 T) to investigate the effects of age on regional cerebral volumes and on the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. Increasing age was associated with (1) decreasing volumes of the cerebral hemispheres (0.23% per year), the frontal lobes (0.55% per year), the temporal lobes (0.28% per year), and the amygdala-hippocampal complex (0.30% per year); (2) increasing volumes of the third ventricle (2.8% per year) and the lateral ventricles (3.2% per year); and (3) increasing odds of cortical atrophy (8.9% per year), lateral ventricular enlargement (7.7% per year), and subcortical hyperintensity in the deep white matter (6.3% per year) and the pons (8.1% per year). Many elderly subjects did not exhibit cortical atrophy or lateral ventricular enlargement, however, indicating that such changes are not inevitable consequences of advancing age. These data should provide a useful clinical context within which to interpret changes in regional brain size associated with "abnormal" aging.

Adult↗

Occupational injuries: a study of health care workers at a northwestern health science center and teaching hospital.

1. This retrospective study examined the magnitude of the problem of work related health hazards affecting professional and non-professional employees of a state university health science center and hospital. 2. From the 1,513 injury episodes that occurred among the 9,668 employees during the 32 month study period, it was determined that the highest risk categories for both department and job were nursing, housekeeping, food service, and laboratory technicians. 3. Injury rate for females (11.2 per 100 person years) was more than twice that of males (5.1). Injury rates declined from 11.6 per 100 person years at ages 25 to 39 to 3.8 at ages over 60. Puncture wounds (32.7%), mostly by needlesticks, were the most frequently reported injury type, followed by strains and sprains (17.2%), lacerations (12.5%), and contusions (12.1%).

Academic Medical Centers↗

Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias.

In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias.

Adult↗

Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy.

OBJECTIVE: To test the hypothesis that propafenone, administered orally, prevents symptomatic paroxysmal supraventricular arrhythmias. DESIGN: a 6-month, open-label, dose-finding phase followed by a randomized, double-blind, placebo-controlled, crossover phase, with each treatment period lasting up to 60 days. SETTING: An outpatient clinic. PATIENTS: Thirty-three patients with either paroxysmal supraventricular tachycardia (n = 16) or paroxysmal atrial fibrillation (n = 17) were enrolled. Their arrhythmias were documented by electrocardiogram before enrollment. Twenty-three patients (14 with paroxysmal supraventricular tachycardia and 9 with paroxysmal atrial fibrillation) were randomized and the data obtained from these patients were used in the efficacy analysis. INTERVENTION: Propafenone (300 mg three times daily in 19 patients, 300 mg twice daily in 3 patients, and 150 mg twice daily in 1 patient) and matching placebo tablets were administered in a randomized sequence. MEASUREMENTS: Symptomatic arrhythmia was documented by telephone transmission of the electrocardiogram. MAIN RESULTS: The time to first recurrence was prolonged for the overall group of 23 patients while they received propafenone (P = 0.004). The recurrence rate of arrhythmia during treatment with propafenone was estimated to be approximately one fifth of the recurrence rate during treatment with placebo. CONCLUSIONS: Propafenone is effective in reducing symptomatic paroxysmal supraventricular arrhythmias.

Adult↗

Brain anatomic effects of electroconvulsive therapy. A prospective magnetic resonance imaging study.

To determine prospectively whether electroconvulsive therapy (ECT) produces structural brain changes, 35 inpatients with depression underwent magnetic resonance imaging before and twice after (at 2 to 3 days and at 6 months) completion of a course of brief-pulse, bilateral ECT. The magnetic resonance images were analyzed blindly for evidence of changes in brain structure using two approaches: measurement of regional brain volumes and a pairwise global comparison. Structural brain abnormalities were present in many patients before ECT. The course of ECT produced no acute or delayed (6-month) change in brain structure as measured by alterations of the total volumes of the lateral ventricles, the third ventricle, the frontal lobes, the temporal lobes, or the amygdala-hippocampal complex. In five subjects, the pairwise global comparisons revealed an apparent increase in subcortical hyperintensity, most likely secondary to progression of ongoing cerebrovascular disease during follow-up. Our results confirm and extend previous imaging studies that also found no relationship between ECT and brain damage.

Amygdala↗

Occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia due to atrioventricular nodal reentry.

The occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia (PSVT) has been well documented when PSVT is secondary to atrioventricular reentry, but not when PSVT is secondary to atrioventricular nodal reentry (AVNRT). Seventeen patients with AVNRT were followed using transtelephonic electrocardiogram monitoring to document symptomatic tachycardias. The median length of telephone monitor surveillance was 357 days. Fifteen of 17 patients transmitted electrocardiograms that showed PSVT. Three of 17 patients (18%) transmitted electrocardiograms that showed atrial fibrillation. A transition from PSVT into atrial fibrillation was not recorded, but all three did have PSVT recorded on other days of follow-up. We report the occurrence of atrial fibrillation in patients with AVNRT and that its incidence is higher than expected for the general population.

Atrial Fibrillation↗