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Biomedical subjects

R S Lees

Publications and source records attributed to R S Lees.

At least 55 records · Page 3Linked to original sources

Noninvasive diagnosis of extracranial cerebrovascular disease.

Noninvasive methods for diagnosis of carotid and vertebrobasilar disease may be divided into passive techniques and those in which the body is interrogated by the introduction of some sort of signal such as an ultrasound beam. Older techniques have been of limited value, whereas newer noninvasive methods can give specific, accurate, and quantitative information as to the location and extent of arterial stenosis.

Carotid Artery Diseases↗

Transmural [125I]albumin concentration in the rabbit aorta during acute hypoxia.

We have quantified the concentration profile of 125I-labeled rabbit albumin in the avascular intima and media of the rabbit descending thoracic aorta following intravenous injection under control and acute hypoxic conditions in vivo. Our purpose was to determine if alterations occurred in the transmural concentration profiles which could be attributed to hypoxia-induced changes in the permeability of the intimal endothelium to plasma-borne macromolecules. The profiles were obtained with frozen serial sections of the aorta from experiments of 30 min duration. Acute hypoxia was induced by addition of nitrogen to the breathing mixture. The hypoxia resulted in arterial pO2 values of 23--32 mm Hg while the arterial pO2 in the control animals ranged from 80 to 88 mm Hg. All animals were under sodium pentobarbital anesthesia. The results revealed no detectable changes in the concentration profile in the inner media accompanying hypoxia. However, increases in the label concentration in the outer media of the hypoxic animals suggested either dilation or increased permeability of the adventitial blood vessels.

Animals↗

Adrenal cortical function in homozygous familial hypercholesterolemia.

The biosynthesis of adrenal corticosteroids requires a supply of cholesterol that can be derived from both local synthesis and uptake of plasma lipoproteins. Recent studies have provided evidence that receptor-mediated uptake of low density lipoproteins provides an important source of cholesterol for corticosteroid synthesis by human adrenocortical cells that are grown in tissue culture. In the present study we have examined parameters of adrenocortical function in three patients with homozygous familial hypercholesterolemia (two receptor negative, one receptor defective) to assess whether a decreased number of LDL receptors, measured in vitro, influences in vivo corticosteroid production under basal conditions and in response to prolonged stimulation with ACTH. Basal adrenocortical function (assessed by the serum concentrations of cortisol and ACTH plus urinary excretion of 17 OHCS, 17 KS, and urine-free cortisol) was normal in all three patients. Stimulation with intravenous ACTH resulted in rapid increases in the serum concentrations of cortisol in all patients. Plateau concentrations of cortisol during prolonged ACTH stimulation were lower in the two receptor-negative patients (36 to 41 micrograms/dl) but all subjects had at least a threefold increase over basal values. Excretion of urine-free cortisol was reduced in both receptor-negative patients (33% to 36% of controls); this was paralleled by decreased excretion of 17 KS in both patients and of 17 OHCS in one patient. Urine-free cortisol excretion was reduced in the receptor-defective patient (57% of controls), but excretion of 17 OHCS and 17 KS was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Low density lipoprotein degradation by mononuclear cells from normal and dyslipoproteinemic subjects.

Three major characteristics of cell surface low density lipoprotein (LDL) receptor activity in fibroblasts or lymphocytes are high-affinity LDL binding or degradation, specificity for LDL, and "inducibility"--that is, the ability to increase when cells are cultured in the absence of lipoproteins. Cells from patients with receptor-negative homozygous familial hypercholesterolemia (FH) have been reported to express none of these characteristics, and the patients are thought to have a genetic absence of LDL receptors. We found that, although induced receptor-negative lymphocytes degraded less LDL than did normal lymphocytes, the curves for LDL degradation versus LDL concentration were biphasic, with greater concentration-dependence at LDL concentrations less than 60 micrograms/ml, indicating high-affinity LDL degradation. The percentage of specific LDL degradation by induced receptor-negative lymphocytes was two-thirds of normal with LDL at 10 micrograms/ml and increased to normal at 50 micrograms/ml, an LDL concentration still within the range of high-affinity degradation. Receptor-negative lymphocytes could be induced by incubation in the absence of lipoproteins to degrade twice as much LDL as they did when freshly isolated. Freshly isolated cells from abetalipoproteinemic patients and one receptor-negative patient degraded as much LDL as did fresh normal cells. The findings indicate that receptor-negative lymphocytes have a mechanism for facilitated uptake of LDL that resembles that of normal lymphocytes, although it is not as efficient.

Abetalipoproteinemia↗

Detection of aortic porcine valve dysfunction by maximum entropy spectral analysis.

A high-resolution method of spectral analysis, of the class generally called "maximum entropy method," was used in a study of aortic porcine valve closing sounds in 37 patients (ages 19 to 76). Spectra from 27 normal xenografts, implanted from 2 weeks to 61 months previously, were characterized by a dominant frequency peak, F1, at 89 +/- 15 Hz (mean +/- SD), with a lower amplitude peak, F2, at 154 +/- 25 Hz. Eight of nine patients with aortic porcine valve dysfunction were proved surgically to have leaflet degeneration or infection and had either F1 (139 +/- 54 Hz) and/or F2 (195 +/- 74 Hz) significantly higher than normal (p less than .001). In two patients with paravalvar leak but no leaflet abnormality, F1 and F2 were in the normal range. Estimation of F1 and F2 was highly reproducible and was unaffected by duration of implant up to 5 years. Spectral analysis of aortic porcine valve closing sounds by the maximum entropy method may be useful for detection of intrinsic xenograft dysfunction.

Adult↗

Selective accumulation of low density lipoproteins in damaged arterial wall.

To determine whether damaged arterial wall selectively accumulates lipoproteins, normocholesterolemic rabbits were injected with human radiolabeled low density lipoproteins, high density lipoproteins, and/or albumin 24 hr to 12 weeks after balloon-catheter de-endothelialization of the abdominal aorta. When 125I-labeled low density lipoproteins and 99mTc-labeled albumin were injected simultaneously, the amount of 125I-low density lipoprotein present 24 hr later in abdominal aortas increased steadily, for several weeks, above the amount present at 24 hr in control animals. The increase correlated closely with the degree of re-endothelialization and correlated closely with the degree of re-endothelialization and reached an average maximum for the whole abdominal aorta of three times control when re-endothelialization was between 75 and 85% complete. By contrast, the amounts of 99mTc-albumin or 125I-labeled high density lipoprotein in balloon-damaged abdominal aortas, and the amounts of 125I-low density lipoprotein, 125I-high density lipoprotein, or 99mTc-albumin in undamaged thoracic aortas of injured animals showed no such increase. As early as 2 weeks after de-endothelialization, en face radioautographs made following injection of 125I-labeled low density lipoproteins revealed localized areas of greatest radioactivity around the leading edges of regenerating endothelial islands, broad areas of intermediate radioactivity corresponding to the de-endothelialized areas, and very like radioactivity in the re-endothelialized areas. This pattern occurred rarely with 125I-labeled high density lipoproteins and not at all with 125I-labeled albumin. The results suggest that low density lipoproteins are selectively accumulated by the healing rabbit aorta and that the accumulation is greatest in regions where the endothelium is actively regenerating.

Albumins↗

External imaging of human atherosclerosis.

Autologous plasma low-density lipoproteins labeled with I-125 were used as a tracer to identify atherosclerotic lesions in the carotid arteries of the neck. Following intravenous injection of I-125-LDL, images were made at intervals from 6 to 36 hr with the gamma camera in three patients with known carotid disease and one control subject. The carotid lesions, confirmed by angiography, were imaged successfully in all three patients, whereas no focal LDL accumulation was visible in the carotid arteries of the control subject. The findings suggest that it may be possible to image atherosclerosis externally and thus to follow the course of the disease.

Angiography↗

The effect of angiotensin II on in vivo albumin transport in normal rabbit aortic tissue.

Angiotensin II and other vasoactive amines may have a direct effect on the permeability of the arterial wall. We have investigated the effect of angiotensin II in vivo albumin transport across the aortic wall in rabbits following intravenous injection of [125I]albumin. Transmural concentration profiles of 125I-labeled albumin across the intima and media of the aorta, generated during 25 min of either angiotensin or saline infusion, were measured by a serial-sectioning technique. The uptake of labeled albumin through the aortic wall was found to be dependent on position and to increase from the descending thoracic up to the arch. Angiotensin infusion increased albumin uptake in the region of the aorta proximal to the first pair of intercostal arteries and magnified the position dependence. Angiotensin infusion did not change the uptake of albumin in the descending thoracic aorta between intercostal arteries. The arterial blood pressure elevation associated with angiotensin infusion was not of prime importance in producing the uptake patterns described above.

Angiotensin II↗

Imaging of acute arterial injury with 111In-labeled platelets: a comparison with scanning electron micrographs.

The relationship between degree of acute arterial injury, extent of platelet deposition, and ability to visualize arterial injury with Indium 111-labeled platelets was studied in 18 rabbits. An aortic lesion was made with a balloon catheter in each animal immediately after injection of autologously labeled platelets. Three nonlesioned rabbits with 111In-labeled platelets served as controls. An additional control study was performed in 12 lesioned rabbits in which nine were injected with 111In-labeled plasma protein and three with 111In-labeled red blood cells. A postmortem scanning electron microscope study of the aortae was made to determine the degree of injury to the intima and the amount of platelet deposition on the damaged arterial wall. The radionuclide scans and scanning electron micrographs were then compared. Lesions were seen in ten of 18 animals with labeled platelets that had extensive regions of denuded endothelium covered by a contiguous layer of platelets. Lesions consisting of patchy deendothelialization and platelet deposition could not be visualized on the scans. Red blood cells and fibrin were not conspicuous on micrographs of the lesions. No lesions were visualized in animals receiving 111In-labeled plasma protein or red blood cells before arterial injury, despite platelet deposition in the lesions.

Animals↗

Duplex Doppler scanning and spectral bruit analysis for diagnosing carotid stenosis.

Spectral phonoangiography provides accurate quantitative noninvasive assessment of carotid stenosis, but only when a carotid bruit is present. Duplex Doppler ultrasound scanning permits imaging of the carotid bifurcation and qualitative assessment of the extent of carotid stenosis. Using these two methods and commercial equipment, we compared the noninvasive results with results of carotid angiograms performed within 2 weeks of the noninvasive studies. Of 299 vessels (common, internal and external carotid) assessed by both methods in 50 unselected patients, the noninvasive combination gave results correct to within 1 mm of the angiographic value in 95% of the vessels studied. These two noninvasive methods in combination allow diagnosis and follow-up of carotid stenosis with accuracy comparable to that of angiography in patients with and without carotid bruits.

Angiography↗

Correlation of spectral phonoangiography and carotid angiography with gross pathology in carotid stenosis.

Spectral phonoangiography, a noninvasive method for measurement of the residual-lumen diameter of carotid stenosis by bruit analysis, was compared with x-ray angiography and direct measurement of the pathological specimen at carotid endarterectomy in 39 bifurcations from 36 patients. In six studies, the bruit was too faint to analyze. In 31 of the other 33 studies, the phonoangiogram predicted the residual-lumen diameter to within 0.5 mm of the measured value. Of the 39 contrast angiograms, 35 showed residual lumens within 0.5 mm of the value measured in the specimen, two showed lumens between 0.5 and 1 mm, and the sizes of two could not be estimated because of vessel overlap in all planes. Spectral phonoangiography and contrast angiography are both accurate methods for evaluation of carotid stenosis. Since phonoangiography is noninvasive, it may be of particular value in determining the natural history in patients with carotid bruits.

Auscultation↗