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Biomedical subjects

M R Freeman

Publications and source records attributed to M R Freeman.

At least 109 records · Page 6Linked to original sources

Effects of subsidising bus travel on the occurrence of road traffic casualties.

Between 1975 and 1 April 1986, public transport by bus in the metropolitan county of South Yorkshire, England, was increasingly subsidised. Trends in road traffic accident casualties between 1974 and 1983 in all the six provincial English metropolitan counties have been compared in order to examine the possible effect of this unique subsidy on the incidence of road traffic accident casualties. During that period the total number of casualties in South Yorkshire did not change significantly compared to the other metropolitan counties. However, the proportion of all casualties in South Yorkshire who were bus occupants did increase relative to other metropolitan counties, indicating either an increase in the amount of bus travel or a decrease in travel by other modes. There was a large increase in bus patronage in South Yorkshire relative to the other metropolitan counties, and the conclusion is that it is the transport policy in South Yorkshire which resulted in an actual increase in distances travelled by bus. Since bus is the safest form of road travel, it is concluded that the public transport subsidy in South Yorkshire has benefited the health of the local population by providing the social amenity of additional travel at the least additional health cost.

Accidents, Traffic↗

Quantitative analysis of stress thallium-201 myocardial scintigrams: a multicenter trial.

Previously we validated a method for quantification of 201TI myocardial stress distribution and washout in which the patient's stress and washout circumferential profiles are compared with observed normal limits. The present study reports the results of a multicenter trial in which this method, utilizing normal limits from our institution, was employed to evaluate the presence, location, and extent of coronary artery disease (CAD). The normal limits utilized were generated from 49 patients having a low likelihood of CAD. The study population included 157 patients from four centers in the United States and Canada as well as a comparative prospective population from Cedars-Sinai Medical Center (CSMC) of 51 patients with CAD, 30 patients with normal coronary arteriograms, and 30 additional low-likelihood normals. The results in the combined centers regarding overall detection of CAD revealed a sensitivity of 84% and a frequency of test normality in the patients with low likelihood of CAD of 88%, compared to a sensitivity of 82% and true normalcy rate of 83% obtained in the prospective CSMC population. The sensitivity for detecting disease increased according to the extent of angiographic CAD in both the multicenter sites and the prospective CSMC group. Regarding localization of disease, similar sensitivities and specificities for detecting disease in individual coronary arteries were found in the multicenter sites and the prospective CSMC population. The results indicate that our method for quantifying 201TI stress-redistribution scintigrams utilizing standard normal limits can be applied at other institutions using a variety of scintillation cameras with similar accuracy to that currently obtained at our institution.

Adult↗

Lipoprotein lipase and hepatic lipase deficiencies associated with impaired chylomicron clearance in D-(+) galactosamine hepatitis.

D-(+) galactosamine (GaIN) produces a reversible from of hepatic injury in the rat, accompanied by alterations in morphology and composition of plasma lipoproteins in the fasting state. Lipoprotein lipase (LPL) and hepatic lipase (HL) activities were measured in fasting control and GaIN rats 24 hr after GaIN injection and initiation of fasting. Significant (p less than 0.001) deficiencies of both enzymes were noted in GaIN animals as compared to controls with LPL activity decreasing to 37.6% and HL activity to 23.2% of control values in GaIN animals. Serial enzyme determinations performed in both GaIN and control animals after gastric fat loading revealed an early persistent HL deficiency (p less than 0.025) at 9 hr after GaIN injection and initiation of fasting which persisted after the fat loading at 15 hr, and a later appearing LPL deficiency (p less than 0.025) was noted at 24 hr after GaIN injection and at 9 hr after fat loading. Serial compositional studies of plasma lipoproteins in pooled specimens after a gastric fat load revealed a marked chylomicronemia in GaIN animals compared to controls which reached a maximum at 12 hr after fat loading. A slight increase in VLDL (very low density lipoprotein) triglyceride and total cholesterol (CH) and a late-appearing (16 hr after fat loading) LDL (low density lipoprotein) CH peak, consisting mostly of unesterified CH, were also noted in GaIN rats as compared to control animals. These data demonstrate a defect in chylomicron (CM) catabolism in GaIN hepatopathy in the rat which is probably secondary to the observed severe LPL and HL deficiencies, although other factors such as activator deficiency, plasma inhibitory substances, and a defective CM particle may be important.

Animals↗

Improved assessment of inferior segmental wall motion by the addition of a 70-degree left anterior oblique view in multiple gated equilibrium scintigraphy.

Conventional anterior and 45-degree left anterior oblique (LAO) views are limited in the evaluation of inferior segmental wall motion by multiple gated equilibrium cardiac blood pool scintigraphy. This study evaluated the addition of a 70-degree LAO view by comparing scintigraphic and contrast ventriculography in 25 patients, of whom 17 demonstrated abnormal inferior wall motion. Abnormal inferior wall motion was correctly identified in only 10 of 17 patients in the anterior view, but in 16 of 17 patients in the 70-degree LAO view. The number of assessable inferior segments was improved from 58% in the anterior view to 98% in the 70-degree LAO view. When the inferior segments could be visualized in the anterior view, inferior wall motion was accurately assessed. The addition of the 70-degree LAO view aids in the multiple gated equilibrium scintigraphic detection of inferior wall motion abnormalities with a minor loss in specificity.

Adult↗

Comparison of upright and supine bicycle exercise in the detection and evaluation of extent of coronary artery disease by equilibrium radionuclide ventriculography.

Upright and supine multiple gated cardiac blood pool scintigraphy was performed at rest and during maximum exercise in 37 patients, 15 with normal coronary arteriograms, 12 with coronary artery disease (CAD) without myocardial infarction (MI), and 10 with CAD and previous MI. Heart rate and systolic blood pressure were similar during upright and supine exercise in normal patients, but were significantly lower during supine exercise in both CAD groups. Left ventricular (LV) ejection fraction (EF), right ventricular (RV) EF, and LV segmental wall motion were similar in the upright and supine positions at rest or during maximum exercise within each group and showed high concordance of exercise responses. Although LV end-diastolic volume increased in all three groups during upright exercise and in both CAD groups when exercised supine, it did not change during supine exercise in patients without CAD. The fall of LV end-systolic volume in normals was greater during supine exercise than during upright exercise. LV end-systolic volume rose in the CAD patients in both positions. Therefore, although LVEF, RVEF, and LV segmental wall motion responses are similar in the upright and supine positions, LV end-systolic and LV end-diastolic volume changes are not. For detecting and evaluating CAD, the two different positions of exercise appear to have similar diagnostic content.

Coronary Circulation↗

Improvement in global and segmental left ventricular function after coronary bypass surgery.

Ventricular function was assessed at rest and during exercise by multiple gated cardiac blood pool scintigraphy before and after coronary artery bypass surgery in 21 patients. Resting left and right ventricular ejection fraction and segmental wall motion were unchanged by surgery. However, the postoperative exercise response of left ventricular ejection fraction (-1 +/- 12% vs 6 +/- 9%) and segmental wall motion score (medium -2.7 [range -8 to 2] vs -0.4 [range -6 to 2]) were significantly improved (p less than 0.05). The normal right ventricular ejection fraction exercise response was maintained after surgery. Previous myocardial infarction in 15 patients did not attenuate the observed improvement in ventricular function. In addition, normal postoperative left ventricular ejection fraction response to exercise was associated with symptomatic improvement. In three of six patients a normal preoperative left ventricular ejection fraction response to exercise was not maintained. Therefore, global and regional left ventricular reserve is improved by coronary bypass surgery and this improvement is not affected by previous myocardial infarction.

Adult↗

Progesterone-binding components of chick oviduct: partial purification and characterization of a calcium-activated protease which hydrolyzes the progesterone receptor.

A calcium (Ca2+)-activated protease has been purified from laying hen oviducts. This enzyme can catalyze the limited proteolysis of the native chick oviduct progesterone receptor subunits, A and B, to smaller hormone-binding fragments. The protocol used has resulted in a 2000-fold purification of the enzyme in 40% yield from hen oviduct postmitochondrial supernatant fractions. This resulted in an active, purified protease preparation which can be used as an analytical tool for studying receptor protein structure. Characterization of the purified enzyme has shown that it is activated by Ca2+ (0.5-1 mM), has a molecular weight of 113 000, and has a sedimentation value of 6 S. No effect of calmodulin (Ca2+-dependent regulator) could be shown on the enzymatic activity of the protease. The enzyme has a Km of 1.04 x 10(-8) M for the receptor protein substrate. The protease is inactivated by sulfhydryl attacking reagents and thus can be classified as a sulfhydryl protease. This protease exhibits remarkable similarities to the "receptor transforming factor (RTF)", a Ca2+-activated protease which performs a limited proteolysis on the calf uterine estrogen receptor [Puca, G. A., Nola, E., Sica, V., & Bresciani, F. (1977) J. Biol. Chem. 252, 1358].

Animals↗

Lipoprotein metabolism in liver disease.

In this review we have endeavored to emphasize the central role of the liver in normal lipoprotein metabolism and to demonstrate how derangements in these metabolic processes can lead to abnormalities characteristic of liver disease. Since changes in the concentration and composition of plasma lipids and lipoproteins occur frequently in liver disease, these findings may be useful in following the clinical course of patients with liver disease of various causes. It should be emphasized that elevated plasma triglycerides and cholesterol are due to underlying defects in lipoprotein metabolism and should not be confused with primary hyperlipidemia. Impaired cholesterol esterification, abnormal lipoprotein electrophoretic patterns and lipoprotein compositional changes, all reflect abnormalities of lipoprotein metabolism that are secondary to hepatocellular injury or cholestasis. These abnormalities are very sensitive indicators of fundamental metabolic defects that are related in part to LCAT and apoprotein activator deficiencies, impaired H-TGL and LPL activity and, perhaps, defective remnant lipoprotein clearance by the liver. Since these abnormalities tend to improve with clinical recovery they have proved to be reliable and sensitive indicators of hepatic function and thus, are useful in the assessment of liver disease.

Cholestasis↗

Propranolol withdrawal in angina pectoris: a prospective study.

In a prospective study, 100 consecutive patients (mean age 51.3 years) with angina pectoris had propranolol abruptly discontinued 24 to 144 hours (mean 39.0 hours) prior to elective coronary arteriography. The mean duration of therapy was 8.2 months and the mean daily propranolol dose was 216.1 mg. New York Heart Association Class II, III and IV symptoms were present in 30, 41, and 29 patients and one, two, or three coronary arteries were more than 50 per cent narrowed in 37, 29, and 34 cases, respectively. Three patients experienced minor increases in chest pain and two suffered non-transmural myocardial infarctions prior to the time of scheduled cessation of therapy. The same number of minor and major complications occurred in the post-withdrawal period. All four patients who developed non-transmural myocardial infarction in this study had pre-existing Class IV symptoms. The course of the remaining 90 patients was uneventful. These findings do not support the concept of a rebound propranolol withdrawal reaction.

Adult↗

Alpha-adrenoceptor-mediated coronary artery spasm.

Selective coronary arteriography performed on a 41-year-old woman with angina pectoris demonstrated proximal stenosis of the right and left main coronary arteries that was unaffected by nitrate therapy. To exclude coronary artery spasm, the study was repeated, and a striking increase in the narrowing of the right coronary artery was observed. This 90% stenosis was virtually abolished by pretreatment with intravenously given phentolamine hydrochloride. Prolonged alpha-adrenoceptor blockade with phenoxybenzamine hydrochloride improved the patient's exercise tolerance and postexercise electrocardiographic abnormalities when compared to therapy in matched controls given placebo. These observations suggest that alpha-adrenoceptor-mediated coronary artery spasm may mimic organic lesions at coronary arteriography and may be a factor in the pathogenesis of angina pectoris in some patients.

Adrenergic beta-Antagonists↗

Randomness, redundancy and repair: roles and relevance to biological aging.

In this paper, some of the key findings of the last decade will briefly be surveyed and, where possible, be related to two separate computer simulation models which have been designed to determine the validity of certain widely accepted dogmas and to define the limits and restrictions imposed by attrition of or ambiguity of information retrieval from information storage systems. It is known: (1) that the idealized rectangular survival curve in an "ideal" environment is an extrapolation that is inconsistent with reasonable primary assumptions; (2) that loss of redundant copies of functional "housekeeping" genes may well be a dominant contributor to human senescence; and (3) that redundancy, particularly of informational storage, not only confers greater stability on an organism in dealing with stochastic or programmed age changes, but that it also provides a means through which a more optimized use of informational storage space may be attained.

Aging↗

Northern exposure: nuclear cardiology in the Canadian health care system.

The Canadian health care system may provide valuable insights into the future practice of nuclear cardiology in the United States. Rationing of medical care is not legislated by the Canadian health care system, although resource allocation is required of Canadian physicians and hospital administrators. Canadian nuclear cardiologists and physicians are not restricted in the ordering of diagnostic studies, despite the decreased availability in imaging systems and the centralization of equipment and personnel in Canada. Canadian imaging equipment is, in general, used more with less average idle time per unit. Delays in the performance of nonemergent imaging studies are more common in Canadian imaging laboratories. The number of out-of-hospital nuclear medicine laboratories is not increasing, because of government constraints on licensing and the general requirement that only radiologists or certified nuclear medicine physicians can operate these laboratories. A survey of 71 nuclear cardiology laboratories in the United States and Canada reveal that 21% of all cardiac imaging studies are performed for post-myocardial infarction risk stratification in Canada, compared with only 11% in United States laboratories. Rest and reinjection thallium imaging studies are performed more than twice as often in the United States laboratories. Canadian laboratories perform a higher average number of myocardial perfusion (2123 vs 1789) and ventricular function (773 vs 554) studies as compared with their United States counterparts. No other significant differences in clinical usage patterns were identified. A total of 130,000 nuclear cardiologies were performed in Canada in 1993, with less than 5% growth in the number of Canadian studies projected for 1994. Forty-five percent of Canadian perfusion studies are performed with 99mTc-labeled sestamibi frequently using a 2-day protocol (60%) with electrocardiogram gating (30%). Positron emission tomography (PET) can be performed in only six Canadian cities. Canadian PET centers are government funded, located in university teaching hospitals, and principally used for the purpose of research. Stress echocardiography is not widely performed in Canada because of the heavy clinical volume of standard echocardiographic studies at most hospitals, which reduces the time available for stress echocardiography. No separate billing code is available for stress echocardiography studies in Canada. Canadian cardiologists have accepted the value of rest and stress nuclear studies for the management of their patients and have concluded that it is more time efficient to perform clinical duties in lieu of stress echocardiographic studies. In conclusion, the realities of the Canadian health care system are that universal health care is valuable as long as it is consistent high quality medical care, and that the cost of universal coverage must be borne by the taxpayer using the system. The fact that nuclear cardiology has continued to thrive in the Canadian health care system suggests that future health care modifications in the United States will not exert a significant impact on the practice of nuclear cardiology.

Canada↗

Clinical comparison of 180-degree and 360-degree data collection of technetium 99m sestamibi SPECT for detection of coronary artery disease.

BACKGROUND: With multihead gamma cameras both 180- and 360-degree acquisitions of myocardial perfusion are feasible. However, with 99mTC-labeled sestamibi (99mTC-sestamibi) the optimal clinically relevant demonstration of the superiority of 180- versus 360-degree data acquisition has not been performed. METHODS: Seventy-two consecutive patients undergoing 99mTC-sestamibi imaging at rest and stress who had coronary angiography performed within 3 months were enrolled. The results of blinded interpretation of 13 segments per patient for the 180- and 360-degree data were compared for interobserver variability. Sensitivity and specificity of defect localization in the left anterior descending, right coronary, and left circumflex territories for detection of 50% or greater or 70% or greater stenoses by coronary angiography were compared. RESULTS: There was significant segmental agreement of the stress perfusion images between observers for 180-degree (Kappa = 0.63) and 360-degree data (Kappa = 0.58), but the agreement was significantly higher for 180-degree data (p < 0.05). Overall sensitivity for the detection of coronary artery disease as a 50% or greater stenosis in 62 patients was 79% with 180-degree acquisition and 77% with 360-degree acquisition. The specificity for absence of coronary artery disease in 10 patients was also similar at 70% and 80%, respectively. There was no overall difference in detection of individual stenoses with a sensitivity of 54% with 180-degree acquisition and 50% with 360-degree acquisition. Specificity was also similar at 78% and 81%, respectively. CONCLUSION: There is no difference in clinically relevant detection of overall coronary artery disease or individual stenoses using 180- or 360-degree acquisition of 99mTC-sestamibi myocardial perfusion images. However, 180-degree acquisition has superior interobserver reproducibility.

Coronary Angiography↗

Prognostic value of dipyridamole SPECT imaging in low-risk patients after myocardial infarction.

BACKGROUND: The prognostic value of perfusion imaging was assessed in low-risk patients after myocardial infarction (MI) and compared with clinical and angiographic variables. METHODS AND RESULTS: Rest thallium and dipyridamole technetium 99m sestamibi single photon emission computed tomography imaging was performed in 203 (91%) low-risk patients 3 to 21 days after MI who were enrolled in a trial of low-dose warfarin sodium and aspirin. Patients were considered low risk with planned nonintervention, on the basis of an uncomplicated course after MI, negative submaximal stress electrocardiography, and the absence of significant angiographic disease requiring revascularization. During a minimum follow-up of 12 months, 69 patients (34%) had clinical events: 1 cardiac death, 7 MIs, 26 admissions for unstable angina, 18 coronary bypass grafting, and 17 angioplasty. Univariate analysis identified the extent of significant angiographic stenoses (> or =70%) and the extent of scintigraphic defect as predictive of future events. On multivariate analysis, the presence of any scintigraphic reversibility had the strongest correlation with clinical events, with better predictive value than angiographic multivessel stenoses (P =.0006 vs P =.003). CONCLUSIONS: In the low-risk population after MI, scintigraphic reversibility remains a strong predictor of cardiac events, with greater prognostic value than angiographic data. The extent of scintigraphic reversibility was directly correlated with clinical events. Therefore scintigraphic imaging remains clinically relevant for risk stratification in the current low-risk population after MI.

Adult↗

Executive and compensatory memory retraining in traumatic brain injury.

A controlled treatment outcome study was conducted comparing the efficacy of memory remediation treatment with no treatment on traumatic brain-injury patients. The memory remediation treatment consisted of both compensatory and executive training skills and was delivered 6 hours weekly over a 2 1/2-week period. Six subjects in the treatment group and 6 subjects in the control group were matched on WAIS-R FSIQ scores, pre-test memory scores and age. Pre- and post-test measures were obtained for both groups on a paragraph memory task. A significant difference was demonstrated between the treatment and control post-test memory scores. The experimental group significantly improved memory scores beyond that of the control group, suggesting that memory remediation is effective for head-injury patients with memory deficits. Discussion of findings and suggestions for further investigation are presented.

Activities of Daily Living↗