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Biomedical subjects

J R Mitchell

Publications and source records attributed to J R Mitchell.

342 records · Page 19Linked to original sources
PubMedDate not supplied

MR multispectral analysis of multiple sclerosis lesions.

Although quantification of the lesion burden from serial MR examinations of patients with multiple sclerosis (MS) is a common technique to assess disease activity in clinical trials, pathologic change may occur within a lesion without a corresponding change in volume. Therefore, measures of lesion volume and composition may improve the sensitivity of detecting disease activity. A new technique has been developed that provides information about the intensity composition of MS lesions in standard spin-echo MR examinations. The new technique is based on the multispectral "feature space" intensity distributions of the lesions and normal tissues. Analysis of MR examinations of materials with known T1 and T2 times showed that feature space position from spin-echo examinations is largely determined from proton density (rho), T2, and the interecho delay. Information about intensity composition was obtained by reducing the multidimensional intensity distribution to one dimension while minimizing the loss of information. This technique was used to analyze eight lesions in standard spin-echo MR examinations of three patients with MS. Lesion distributions were compared between examinations by first calibrating the examinations based on the intensity distributions of cerebrospinal fluid (CSF), an internal reference tissue. Many of the lesion distributions had a distinctive peak at low intensity, corresponding to normal-appearing white matter (WM). Within the lesion distributions, increases in high intensity peaks generally were accompanied by reductions in the WM peak. Serial analysis of the lesion distributions revealed some dramatic fluctuations, even when lesion volume remained constant.

Calibration↗
PubMedDate not supplied

Erythrocyte-sedimentation rate before and after in-vitro defibrination: A rapid and simple method for increasing its specificity.

The erythrocyte-sedimentation rate (E.S.R.) was measured before and after in-vitro defibrination in 107 patients with high E.S.R.S. The reduction in E.S.R. on defibrination correlates with the fibrinogen level while the post-defibrination E.S.R. correlates with the globulin level. The ratio between the post-defibrination E.S.R. and the pre-defibrination, or standard, E.S.R. varies with different diseases; it is highest when an excess of globulins is the cause of the high E.S.R. and lowest when there is an excess of fibrinogen. Measurement of the post-fibrination E.S.R. is quick and easy and may help in the initial investigation of a high E.S.R.

Blood Protein Disorders↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of enalapril in patients with congestive heart failure and patients with hypertension.

The clinical pharmacokinetics and pharmacodynamics of enalapril and its de-esterified active metabolite, MK 422, were determined in eight patients with congestive cardiomyopathy and five patients with hypertension. After administration of single doses of 2.5, 5, and 10 mg enalapril in the congestive heart failure patients and 20 or 40 mg in the hypertensive patients, serum levels and urine elimination of enalapril and MK 422 were determined. Standing and supine heart rate and blood pressure were measured as was ejection fraction in the congestive heart failure group and renin activity, aldosterone levels, and converting enzyme activity in the hypertensive group. Apparent oral clearance after administration of 5 and 10 mg enalapril was lower in the congestive heart failure patients (0.6 +/- 0.2 and 0.7 +/- 0.4 L/min) than after 20 and 40 mg given to hypertensive patients (2.5 +/- 1.3 and 2.7 +/- 2.7 L/min). The elimination of MK 422 was also slower in the congestive heart failure patients (7.8 +/- 5.0 and 6.8 +/- 2.5 h after 5 and 10 mg enalapril, respectively, vs. 4.6 +/- 2.0 and 5.3 +/- 1.1 h after 20 and 40 mg, respectively, in the hypertension group). The enalapril area under the concentration-time curve increased disproportionately to dose increments in both groups, but was more pronounced in congestive heart failure. Twenty and 40 mg enalapril lowered the blood pressure by 2 h after dosing in the hypertension group, and peak effects were seen 4-5 h after dosing. Peak effects correlated with peak serum MK 422 concentrations but not with enalapril (MK 421) levels. Supine heart rates were unchanged after 20 mg, but increased after 40 mg; standing heart rates were transiently increased after 20 and 40 mg enalapril. Blood pressure was not significantly changed in the congestive heart failure group, and cardiac ejection fraction was unchanged. In the hypertension group, renin stimulation and converting enzyme activity inhibition were seen at 4 h and persisted for at least 24 h after administration of 40 mg enalapril. In summary, the clearance of enalapril and elimination of MK 422 was slower in congestive heart failure patients versus hypertensive patients. Therefore, slower onset and longer duration of drug effect might be anticipated in patients with congestive heart failure versus patients with hypertension during enalapril administration.

Adult↗
PubMedDate not supplied

Age-dependence of hypertensive-normotensive differences in plasma norepinephrine.

We compared venous plasma norepinephrine (NE) concentrations in 191 resting, supine patients with essential hypertension and 129 normotensive controls. Among normotensives, plasma NE increased significantly with age, but among hypertensives, no age-related increase occurred, due to relatively high NE values among young hypertensives. When patients and controls less than 40 years old were considered, hypertensives showed significantly higher plasma NE than the controls (317 vs 245 pg/ml, t = 3.15, p less than 0.01); but above the age of 40 years, no significant hypertensive-normotensive difference was obtained. These results, predicted by recent literature reviews, help to resolve the persistent controversy about sympathetic neural activity in essential hypertension, since such activity appears to be abnormal mainly in young patients. The data are consistent with increased sympathetic nervous system activity in the early stages of essential hypertension.

Adult↗
PubMedDate not supplied

Propylbutyldopamine. Mechanism of blood pressure lowering in hypertensive patients.

The effects of propylbutyldopamine ( PBDA ), an analog of dopamine lacking significant vasoconstrictor effects, were examined in seven patients with essential hypertension. Cardiovascular hemodynamics, renal plasma flow, urinary sodium excretion, and the renin-angiotensin-aldosterone system were examined during PBDA infusion both before and after administration of low (8 micrograms/kg) and high (40 micrograms/kg) doses of the dopamine receptor antagonist metoclopramide. Infusion of PBDA at a rate of 20 micrograms/kg/min lowered mean arterial pressure from an average control value of 112 +/- 4 to 94 +/- 3 mm Hg during the last 5 minutes of infusion (p less than 0.01), and increased effective renal plasma flow from 330 +/- 22 ml/min to 591 +/- 46 ml/min (p less than 0.01). Changes in heart rate (+ 16% +/- 5% increase from control values of 77 +/- 3 bpm), urinary sodium excretion (+ 13% +/- 5% increase from control value of 121 +/- 11 muEq/min), plasma renin activity (+ 23% +/- 15% increase over control value of 1.3 +/- 0.3 ng angiotensin I/ml/hr), and plasma aldosterone (+ 26% +/- 12% increase over control value of 17 +/- 6 ng/dl) accompanied PBDA infusion. Pretreatment with metoclopramide at a dose of 8 micrograms/kg prior to PBDA infusion partially blunted the blood pressure reduction produced by PBDA alone (-10% +/- 8% vs -20% +/- 4% compared to control values, p less than 0.1) but had no effect on PBDA -induced increases in renal plasma flow (+ 179% +/- 15% vs + 179% +/- 9% compared to control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

N-Hydroxylation of phenacetin by hamster liver microsomes.

Hamster liver microsomes have been shown to catalyze the N-hydroxylation of phenacetin. The reaction, which requires oxygen and NADPH, is inhibited by a carbon monoxide/oxygen atmosphere, indicating that it is catalyzed by a cytochrome P-450-dependent mixed-function oxidase. The N-hydroxyphenacetin can be further metabolized by the microsomes, and the reaction is inhibited by phenacetin.

Animals↗
PubMedDate not supplied

Male adolescents' concern about a physical examination conducted by a female.

This descriptive study measured degree of concern of 45 healthy male adolescents aged 13 to 17 from three private physicians' offices when they were told that their complete physical examination might be conducted by a female examiner. Degree was measured on a 20-item Likert-type instrument on which areas of concern were categorized as body image, identity, independence, and relatedness. Concern scores were obtained in each of the four categories, and a total concern score was determined. Relationships between the independent variable, age of the participants, and the dependent variables, concerns (body image, identity, independence, relatedness, and total concerns), were determined by Pearson correlations. Relationships were additionally determined between a second independent variable, Tanner stage of physiological sexual development, and the dependent variables. Partial correlation was used to determine relationships between Tanner stage and concerns while holding age constant. As age increased, concerns decreased, and no significant relationship was found between Tanner stage and concerns. Age was such a contributing factor affecting concerns that when partialed out, no significant relationship between Tanner stage and concerns remained. Because female clinicians might expect to seen more concern in younger adolescent males, research is required on how to reduce these concerns.

Adolescent↗
PubMedDate not supplied

Macromolecular binding in assessing drug and chemical-induced tissue lesions.

The general concepts that underlie the use of macromolecular binding in studies of chemical-induced tissue lesions are reviewed. Parameters for studying the formation of chemically reactive metabolites are discussed and the factors that alter the formation and covalent binding of reactive metabolites are selectively emphasized. Some of the experimental work that led to these concepts is presented.

Acetaminophen↗