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Biomedical subjects

M G Bond

Publications and source records attributed to M G Bond.

At least 73 records · Page 4Linked to original sources
PubMed1989

Detection and monitoring of asymptomatic atherosclerosis in clinical trials.

Methods are currently available to noninvasively detect and evaluate asymptomatic atherosclerosis in the carotid artery, and provide a unique opportunity to monitor the effect of medical intervention during the early stages of atherosclerotic progression. When using high-resolution B-mode ultrasound to monitor lesion change over time, it is the reproducibility of measurements at the arterial wall and lumen that defines the confidence of establishing rates of disease progression. Previous studies have demonstrated that, in a research environment using standardized protocols for scanning and interpretation, the absolute difference between blinded replicate measurements of arterial wall thicknesses at sites of lesion is less than 0.2 mm. The Multicenter Isradipine Diuretic Atherosclerosis Study will use high-resolution B-mode ultrasound to determine the effect of isradipine and hydrochlorothiazide on the rate of progression of carotid artery atherosclerosis in hypertensive subjects. Methods for scanning and interpretation of arterial wall thickenings are presented.

Antihypertensive Agents↗
PubMed1988

Multicenter validation study of real-time ultrasonography, arteriography, and pathology: pathologic evaluation of carotid endarterectomy specimens.

The morphologic description and measurements of endarterectomy specimens are usually believed to be accurate and are used as the gold standard against which the findings of diagnostic procedures are judged. Pathology data on 289 endarterectomy specimens from five participating centers and the corresponding angiography and B-mode ultrasonography data provided a basis for scrutinizing the validity of using the morphologic measurements as a standard. Discrepancies of greater than 1 mm between pathology and angiography measurements of minimum residual lumen occurred in 35% of the cases and between pathology and B-mode ultrasonography measurements in 64% of the cases. Discrepancies of greater than 1 mm between pathology- and angiography-measured lesion width occurred in 81% of the cases and between pathology and B-mode ultrasonography measurements in 64% of the cases. The cases representing mismatches of greater than 1 mm at one participating center were subjected to a rigorous review, with remeasurement of all morphologic features, in an attempt to explain the discrepancies. Various types of artifactual distortion of the specimens, the presence of slit-like and occluded lumens that were likely related to loss of perfusion pressure, and an inability to match planes of interrogation used in angiography and B-mode ultrasonography with pathology planes contributed significantly to the existence of mismatches. On the other hand, fixation and decalcification produced minimal and insignificant distortional changes. We conclude that the acquisition of quantitative data from endarterectomy specimens and the acceptance of morphologic data as a standard are limited by a number of problems that can be defined but have been difficult to resolve.

Carotid Arteries↗
PubMed1987

The significance of nuclear diameter in the biologic behavior of thyroid carcinomas: a retrospective study of 127 cases.

The relationship between nuclear diameter and biologic behavior was studied in 127 cases of thyroid carcinoma. Using a sonic digitizer coupled to a minicomputer, nuclear diameters of 200 randomly selected cancer cells from each case (hematoxylineosin-stained paraffin sections) projected at X 400 magnification were traced and averaged. A total of 25,400 measurements were made. The nuclear diameters varied from 4.7 to 13.1 micron. By analysis of variance, the nuclear diameters were significantly different (p = 0.0007) among the four types of thyroid cancers, being largest in the undifferentiated cancers (8.7 +/- 0.8 micron) and smallest in the medullary cancers (6.6 +/- 0.1 micron). Nuclear diameter was also significantly correlated with degree of tumor differentiation (p = 0.002), maximal tumor diameter (p = 0.03), mitotic rate (p = 0.002), and 5-year survival (p less than 0.05) for all types of tumors. The correlation between nuclear diameter and disease stage was significant only for undifferentiated cancers (p = 0.04). No significant correlations were seen between nuclear diameter and duration of disease, sex, or age of the patient.

Adolescent↗
PubMed1987

Multicenter validation study of real-time (B-mode) ultrasound, arteriography, and pathologic examination.

The ability of high-resolution ultrasound, angiography, and pathologic examination of endarterectomy specimens to identify and quantitate atherosclerosis was compared in a five-center study. The carotid bifurcation in 900 patients was evaluated by angiography and ultrasound. In 216 cases, high-quality endarterectomy specimens were available for comparison with the preoperative images. All comparisons were made in a blinded fashion. Results indicate that ultrasound is able to differentiate angiographically normal from abnormal arteries with a sensitivity of 88% (1077 of 1233 arteries) and accuracy of 79% (1251 of 1578 arteries). Angiographic stenoses equal to or greater than 50% diameter were accurately identified by ultrasound imaging in 72% (1133 of 1578 arteries) of cases, and this was improved by the addition of other functional data (i.e., Doppler spectral analysis and oculoplethysmography). There was only modest correlation of absolute measurements of lesion width, minimal lumen, and standard lumen by the two imaging techniques (r = 0.28 to 0.55). Ultrasound measurements of lesion width were on the average 2 mm greater than those of angiography. The lumen averaged 1.5 mm larger when measured by ultrasound techniques. In the subset in which data were available from endarterectomy specimens, ultrasound showed the best correlation with lesion width (mean difference -1.1 mm) and angiography correlated best with minimal lumen (mean difference -0.1 mm). Neither examination consistently identified ulcerated plaques. Although ultrasound imaging alone has limited usefulness in quantitating luminal stenosis, this can be improved by the use of Doppler spectral analysis and oculoplethysmography. Ultrasound is superior to angiography for quantifying atherosclerotic plaque (lesion width) and will be an important tool for further study of atherosclerotic lesions.

Adolescent↗
PubMed1985

Noninvasive assessment of atherosclerosis in nonhuman primates.

Atherosclerosis is a progressive and degenerative disease of the artery wall which begins relatively early in life, years if not decades prior to the onset of clinical signs and symptoms. One of the major challenges which face investigators in this field of research is to establish the validity and reliability of noninvasive methods which can detect atherosclerotic plaques before they become severe enough to result in tissue ischemia, and to determine whether or not atherosclerotic lesions can be monitored both in terms of rate and direction over time. Although several methods of direct arterial visualization are available currently, high-resolution B-mode ultrasound imaging appears to have the most advantages. This technique is noninvasive, relatively inexpensive, and can visualize not only lumen contour and configuration, but also the atherosclerotic plaque in the underlying wall. Preliminary experiments in animal models suggest that lesions as small as 0.5 mm in the carotid arteries can be detected using this method. Whether or not atherosclerotic plaques can be monitored over time, however, has not been demonstrated.

Animals↗
PubMed1985

Reduction in tissue LDL accumulation during coronary artery regression in cynomolgus macaques.

The aim of this study was to determine whether the amount of LDL that had accumulated in the coronary arteries of cynomolgus monkeys during an 18-month period on a hypercholesterolemic (H) diet was reduced during subsequent periods of 6 and 12 months on a normolipemic (N) diet. This was performed by assessing the accumulation of LDL in the left anterior descending (LAD) branch of the left coronary artery within an area 4 mm from its origin, since this region contained the largest lesions in the LAD. LDL accumulation was estimated by measuring the percent cross-sectional area of artery occupied by reaction product depicting apo B by an immunoperoxidase procedure. The following reduction in mean (+/- SD) percent cross-sectional area occupied by reaction product was found in 8 animals on the progression diet (group I), 7 animals on the 6-month regression diet (group II), and 9 animals on the 12-month regression diet (group III), respectively: 21.7 +/- 4.7, 6.9 +/- 5.5, and 2.3 +/- 1.3. Differences between group I and either group II or III were statistically significant (using the Wilcoxon signed-ranks test). In group I, LDL was localized primarily in the necrotic core and around pools of foam cells. In groups II and III fewer foam cells and smaller pools of extracellular debris were qualitatively evident, and LDL was localized closer to the lumen and along collagen fibers. These results suggest that lowering of the plasma LDL level following termination of a hypercholesterolemic diet also induces a decrease in the LDL content in coronary artery lesions, even without significant reductions in lesion size, and that this decrease might be responsible for the decrease in foam cells.

Animals↗
PubMed1985

The significance of mitotic rate: a retrospective study of 127 thyroid carcinomas.

The association between mitotic rate and biologic behavior was studied in 127 cases of thyroid cancer. Based on the observation of 12,700 high-power fields (HPF), the mitotic rate varied from 0 to 316 (33.3 +/- 4.9) mitoses/100 HPF. Mitotic rate differed among the four types of thyroid cancers and correlated inversely with the differentiation of the tumors, being highest (156.8 +/- 32.9) in the undifferentiated tumors and lowest (17.3 +/- 2.4) in the papillary tumors. By analysis of variance (AOVA), the relations between mitotic rate and the sex or age of the patient, maximal diameter of the tumor, and vascular or capsular invasion were assessed, but significant relations were not found (r2 = 44.2 per cent). Follow-up observation, possible in 74 patients, showed mitotic rate to be significantly related to the survival period (Student's t-test; P values ranging from 0.02 to 0.05). The patients who were alive five and ten years after surgery had had lower mitotic rates than those who had died during the same follow-up period. The correlation of low mitotic rate with a high degree of differentiation and low potential for invasion might, in part, explain the better surgical cure rates for papillary thyroid carcinoma than for other types of thyroid cancers.

Adenocarcinoma↗
PubMed1985

Evaluation of upper extremity vasculature with high-resolution ultrasound.

Twenty-eight vascular and perivascular lesions of the upper extremity in 21 patients were studied from August 1982 to December 1982 by means of a 10 MHz real-time B-mode ultrasound unit. They included eight perivascular masses, 16 arterial repairs, and five thrombosed or occluded arteries. Imaging of arteries that ranged in size from a brachial to a digital artery was reliable. Vessels were tracked proximally and distally while changes in wall compliance, luminal diameter, wall diameter, intimal integrity, and luminal compression were observed dynamically. Size, location, acoustic characteristics, and extent of vascular involvement could be determined in cases of perivascular masses. Sonographic findings were confirmed by arteriography, dynamic radionuclide imaging, computerized tomography, or surgical exploration. Ultrasonography eliminated the need for preoperative arteriography in some cases. In no instances were our ultrasonographic impressions in error when correlated with results of more invasive techniques. No adverse effects were encountered. We concluded that real-time 10 MHz ultrasonography is a safe, noninvasive, reproducible, and accurate technique that can be used quantitatively and qualitatively on the upper extremity after surgery to assess patency, pulse dynamics, and anastomotic characteristics of arterial repairs and before surgery to evaluate perivascular masses for acoustic characteristics, location, and influence on adjacent vascular structures.

Adolescent↗
PubMed1984

A study of atherosclerosis regression in Macaca mulatta. V. Changes in abdominal aorta and carotid and coronary arteries from animals with atherosclerosis induced for 38 months and then regressed for 24 or 48 months at plasma cholesterol concentrations of 300 or 200 mg/dl.

Young adult male rhesus monkeys (Macaca mulatta) were fed an atherogenic diet for 38 months. After 38 months of atherosclerosis induction, a baseline group was selected and necropsied to determine the extent and severity of atherosclerosis before regression regimens were begun. The remaining animals were fed diets that varied in cholesterol concentration in order to maintain plasma cholesterol concentrations of approximately 200 or 300 mg/dl for either 24 or 48 months. The progression or regression of atherosclerosis in coronary arteries, abdominal aorta, and carotid arteries was determined by comparing them to the baseline group. Coronary artery atherosclerosis regressed in the majority of animals after 4 years but not after 2 years when plasma cholesterol concentrations were about 200 mg/dl. Among the animals maintained at plasma cholesterol concentrations of about 300 mg/dl, about half the animals progressed in the extent of coronary artery atherosclerosis while about half regressed. The majority of the animals that progressed in lesion extent were genetic hyperresponders to dietary cholesterol whereas those that regressed were predominantly hyporesponders, even though their plasma lipid concentrations were equivalent during the regression phase. The changes seen in atherosclerosis extent in the abdominal aorta were quite similar to the changes seen in coronary arteries. Changes at this site were not pronounced after 2 years, but after 4 years animals with plasma cholesterol concentrations of about 300 mg/dl progressed while the animals at 200 mg/dl were mostly unchanged. No evidence for atherosclerosis regression was found in the common carotid arteries or in the carotid bifurcations.

Animals↗
PubMed1984

Erectile failure in cynomolgus monkeys with atherosclerosis of the arteries supplying the penis.

We evaluated by direction observation the sexual behavior of normal and atherosclerotic adult male cynomolgus monkeys (Macaca fascicularis) toward sexually receptive female cynomolgus monkeys. Marked deficits in erectile and ejaculatory function were found in the atherosclerotic monkeys. These animals were normal in other aspects of social and sexual behavior and had normal concentrations of circulating testosterone. At necropsy, histopathologic evaluation of the urogenital vasculature revealed atherosclerotic lumen obstruction of internal iliac, internal pudendal and penile arteries which apparently resulted in diminished in vivo capacity of these vessels to accommodate the large increases in blood flow required for the production of an erection. These findings provide further evidence for the existence of an association between atherosclerotic obstruction of the internal iliac, pudendal and penile arteries and the occurrence of erectile failure, and suggest the usefulness of the nonhuman primate as an animal model for clinical studies of atherosclerotic sexual dysfunction of man.

Animals↗
PubMed1984

Marked elliptocytosis and schistocytosis in hematopoietic dysplasia.

A 78-year-old white male patient presented with anemia characterized by marked elliptocytosis and schistocytosis. Other morphologic findings in the peripheral blood and marrow were diagnostic of hematopoietic dysplasia (preleukemic syndrome). Five years previously elliptocytosis and schistocytosis were not present, and the only features suggesting hematopoietic dysplasia were significant numbers of micromegakaryocytes in the marrow and rare giant platelets with giant granules in the peripheral blood. The features of this case suggest that acquired marked elliptocytosis and schistocytosis may be an unusual manifestation of hematopoietic dysplasia.

Aged↗
PubMed1984

Pulse wave velocity and morphological changes associated with early atherosclerosis progression in the aortas of cynomolgus monkeys.

To determine the time course of changes in arterial stiffness and corresponding morphology during atherosclerosis progression, we determined pulse wave velocity (PWV) in cynomolgus monkeys fed atherogenic (test) and control diets over an 18-month period. At 6-month intervals, thoracic and abdominal aortic PWVs were determined with a pressure transducer retracted down the aorta in 5 cm increments. Iliac artery PWV was determined from the abdominal aortic pressure to a noninvasive femoral pulse. Groups of individual cardiac cycles, triggered by the ECGs, were sampled on a computer and the velocities (PWV) of the pulse wave fronts were calculated. There was no significant difference between groups until 18 months when test animal PWVs in the thoracic (7.44 +/- 0.83 m X s-1) and abdominal (8.52 +/- 0.67 m X s-1) aorta were significantly greater than those of controls (5.02 +/- 0.51 and 6.24 +/- 0.53 m X s-1, respectively), indicating increased arterial stiffness. There was no change in iliac PWV, 10.96 +/- 0.74 m X s-1 for 18-month test compared with 9.44 +/- 0.89 m X s-1 for controls. Constant infusion of nitroprusside and noradrenaline lowered and raised blood pressure and PWV in all groups, and PWV changes due to drug-induced pressure changes were greater in atherosclerotic than in control arteries. Systolic pressure of 18-month test and pulse pressure of 12- and 18-month test groups were significantly greater than controls under all drug conditions, also indicating increased vessel stiffness. Morphometric evaluation of histological aortic cross sections revealed early, noncomplicated atherosclerosis showing gradual increases in the ratio of intimal to medial cross-sectional area in the thoracic (1.24 +/- 0.30 after 18 months) and abdominal (1.70 +/- 0.42 after 18 months) aortas, compared with control ratios of essentially zero. The fraction of the internal elastic lamina covered with atherosclerotic lesions, and maximal intimal thickness also showed significant increases during the test diet period. These data show that early atherosclerosis resulted in aortic but not iliac stiffening which was detected by increased PWV before development of significant stenotic lesions.

Animals↗
PubMed1984

Physicochemical and histological changes in the arterial wall of nonhuman primates during progression and regression of atherosclerosis.

To identify the temporal changes occurring during progression and regression of atherosclerosis in nonhuman primates, we have studied the physicochemical and histological characteristics of arterial wall lesions during a 30-mo progression period of diet-induced hypercholesterolemia and during a 12-mo period of regression. Three groups of cynomolgous monkeys (Macaca fascicularis) were studied. Control groups were fed a basal chow diet for 18, 24, and 30 mo and were compared with progression groups that were fed a high-cholesterol-containing diet for up to 30 mo. Regression groups were fed a high-cholesterol diet for 18 mo to induce atherosclerosis and then fed monkey chow for up to 12 mo. The progression group monkeys were killed at 6, 12, 18, 24, and 30 mo, and the regression animals were killed at 24 and 30 mo (i.e., after 6 and 12 mo of being fed a noncholesterol-containing chow diet). Histology and morphometry, physical microscopy for cholesterol monohydrate crystals, foam cell and droplet melting points and chemical composition studies were completed on a large number of individual arterial lesions. Control animals had very little cholesterol ester, rare foam cells, and no extracellular cholesterol ester droplets or cholesterol crystals. During progression, the arteries first increased cholesterol ester content to produce high melting (approximately 45 degrees C) foam cell-rich lesions essentially devoid of cholesterol crystals. With time, the number of cholesterol crystals increased so that by 30 mo large numbers were present. Foam cells decreased with time but their melting temperature remained high while that of extracellular droplets fell to approximately 38 degrees C. Between 18 and 30 mo necrosis appeared and worsened. After 6-mo regression, unexpected changes occurred in the lesions. Compared with 24-mo progression, the chemical composition showed a relative increase in free cholesterol, a decrease in cholesterol ester and microscopy revealed large numbers of cholesterol crystals. Concomitantly, foam cells decreased and the melting temperature of both intra- and extracellular cholesterol ester markedly decreased. After 12-mo regression cholesterol decreased, cholesterol crystals and necrosis diminished and collagen appeared increased. Thus, during progression there is initially an increase in the number of foam cells containing very high-melting intracellular cholesterol ester droplets. By 30 mo, cholesterol crystals and necrosis dominate and high-melting foam cells appear only at lesion margins, suggesting that the initial process continues at the lesion edge. The lower melting point of extracellular esters indicates a lipid composition different from intracellular droplets. Thus, the changes observed in these animals generally reflect those predicted for progression of human atherosclerosis. During the initial 6 mo of regression, necrosis remains, the number of foam cell decreases, and cholesterol ester content decreases; however the relative proportion of free cholesterol content increases, and large numbers of cholesterol content are formed. Thus, large and rapid decreases in serum cholesterol concentration to produce regression in fact may result in the precipitation of cholesterol monohydrate and an apparent worsening of the lesions. More prolonged regression (12-mo) tends to return the lipid composition of the artery wall towards normal, partially reduces cholesterol crystals, and results in an improved but scarred intima.

Animals↗
PubMed1983

Platelet-activating factor effects on pulmonary ultrastructure in rabbits.

Morphometric analysis of endothelium in rabbit lungs demonstrated a dramatic effect of platelet-activating factor (PAF) on the ultrastructure of pulmonary vasculature. Plasmalemmal vesicles in capillaries were increased both in size (638 A PAF vs 538 A control) and in number (386/micrograms 3 cytoplasm PAF vs 125/micrograms 3 cytoplasm control) when PAF was administered as a single acute low dose (chi less than 3 micrograms/kg). High concentrations of PAF (chi greater than 3 micrograms/kg) as a single acute dose also increased vesicle number (203/micrograms 3 cytoplasm), but frequently precipitated the respiratory distress syndrome. Chronic administration of PAF with daily doses over periods of either 3.5 or 7 weeks resulted in changes paralleling the acute observations, but did not lead to more extensive lung disease.

Animals↗
PubMed1983

Effects of long-term immunization against the beta-subunit of ovine luteinizing hormone on circulating immune complex formation and on arterial changes in rhesus monkeys.

A major safety issue of contraceptive methods based on long-term immunization is the possible effect of circulating immune complexes (CIC) on the arterial wall. We have measured CIC's in 24 monkeys, immunized against the beta-subunit of ovine luteinizing hormone (oLH beta), emulsified with Freund's complete adjuvant, and in 7 nonimmunized controls by Raji assay, Clq assay, and an assay for rheumatoid factor. Eleven of the 24 immunized monkeys had CIC concentrations that were more than two standard deviations above the mean for controls in at least one of the assays. There was no correlation between antibody titer and CIC. Nine immunized and eight control animals on low-fat diets were killed to evaluate the effects of immunization on the artery wall. The cross-sectional intimal area was measured at several sites from projected microscopic images using a sonic digitizer. No statistically significant differences between test and control groups were found. However, when we compared the upper half of the distribution of test and control animals, we found that the mean intimal area of the thoracic aorta of immunized monkeys was twice that of controls and that that of the abdominal aorta was three times as large. These data indicate that long-term immunization against oLH beta induced CIC's in rhesus monkeys. Small increases in the intimal area were found in about half of the immunized animals. The results of this study suggest the need for a larger, more definitive study in which the diet is manipulated so that plasma lipids mimic those of human females in Western society.

Animals↗
PubMed1983

Apolipoprotein B localization in coronary atherosclerotic plaques from cynomolgus monkeys.

The presence of apolipoprotein B (apo B) was determined in atherosclerotic lesions of coronary arteries from cynomolgus monkeys placed on a hypercholesterolemic diet for one year. Immunofluorescence techniques were applied to sections of arteries that were fixed by perfusion with formalin and embedded in paraffin. Segments of right coronary, left anterior descending, and left circumflex arteries were observed. All segments demonstrated substantial intimal thickening, accompanied by areas of necrosis at the base of the plaque, usually located on the luminal side of the internal elastic lamina. Large clusters of foam cells could be found at the base of such plaques, between intimal smooth muscle cells in the fibromuscular cap, and frequently in the tunica media in regions of necrosis. Immunofluorescence depicting apo B was usually confined to the intima, especially in the necrotic core, but could also be seen in the media in regions in which the internal elastic lamina was missing. Apo B often filled the extracellular space between smooth muscle cells and groups of foam cells but was not identified in the cytoplasm of intact cells. Apo B-positive areas were usually also positive for alcian blue staining, suggesting LDL-sulfated glycosaminoglycan coexistence at such sites. The localization pattern of apo B in lesioned coronary arteries from cynomolgus monkeys was consistent with that found in human coronary lesions, suggesting that diet-induced hypercholesterolemia in such monkeys may be a valid model for studying the role of LDL in human atherogenesis.

Animals↗
PubMed1983

Aneurysms in a large colony of squirrel monkeys (Saimiri sciureus).

This communication reports the findings of a retrospective study of extracranial aneurysms found at necropsy in a large colony of squirrel monkeys (Saimiri sciureus). Eleven (1.5%) of 730 cases had dissecting, saccular, or fusiform aneurysms of the carotid arteries or aorta. Saccular and fusiform aneurysms were found only in animals that had been fed atherogenic diets, whereas dissecting aneurysms occurred in both normo- and hypercholesterolemic monkeys. Neither the type or location of aneurysms, however, could be predicted by the length of time an animal consumed an atherogenic diet, nor by the total mean serum cholesterol concentration. The anatomical characteristics, location, and incidence of aneurysms found in squirrel monkeys resembled closely those observed in human autopsy cases.

Aneurysm↗