Very early aortic responses during atherosclerosis induction in rabbits: measurement by duplex ultrasound. I. Non-invasive study of aortic hyperresponsiveness to serotonin.

We report the use of a non-invasive ultrasound method to visualize and measure changes in serotonin reactivity of the abdominal aorta during the early stages of atherosclerosis development. Studies were performed at 0, 4, 8, and 14 weeks in New Zealand white rabbits fed a diet enriched with 0.5% cholesterol. Change in systolic vessel diameter at each examination was compared with changes in rabbits fed a control diet or rabbits on a diet enriched with cholesterol plus a concentrated marine lipid. After 4 weeks on the diets, the abdominal aortae of rabbit fed the cholesterol-rich diet displayed an enhanced vasoconstriction to serotonin (P less than 0.01). The enhanced vasoconstriction was observed prior to visible morphologic changes, and progressed when restudied at succeeding examinations. Morphologic abnormalities became evident at 8 weeks in cholesterol-fed animals. Dietary supplementation with marine lipid, rich in polyunsaturated fatty acids, diminished the effect of the atherogenic diet on aortic vasoconstriction.

Abnormal serum lipid patterns in primary renal allograft recipients.

The blood lipids profile was determined in 59 patients with successful primary renal allografts, who were followed for an average period of 31.8 months (range, 6 to 80 months). Elevated levels of cholesterol (greater than 250 mg/100 ml) were found in 51% of the patients, elevated levels of triglycerides were found in 56%, and elevated levels of phospholipids in all but one of the patients who were studied (45 of 46). Correlation analysis revealed significant relationships among the systolic blood pressure with total cholesterol (r equals 0.36, P less than 0.01), triglycerides (r equals 0.56, p is less than 0.001), and phospholipids (r equals 0.40, P is less than 0.001). No significant correlations were found between the lipid levels and daily prednisone dosage or with the duration of the period following transplantation. The most significant finding in our study was an elevation of serum phospholipid level--a pattern unreported previously in transplant recipients but which has been reported to be associated with hepatic derangement in nontransplant population. Of 32 patients who had elevated levels of serum phospholipids, the liver function tests were abnormal in 22 patients (69%).

Ultrasound observation on pulsation in human carotid artery lesions.

B-mode ultrasound imaging was used to compare pulsation in moderately advanced, non-calcific, common carotid atherosclerotic lesions with adjacent carotid artery walls where no lesions were visible. Subjects were 13 men with proven coronary atherosclerosis. Average age was 54 years and subjects did not have cerebral symptoms or carotid bruits. Ep, the pressure-strain modulus, was estimated using brachial artery blood pressures recorded on the same clinic visit. Ep values in lesion areas were significantly greater than in nonlesion areas. Two extremely high Ep lesion values were found which could not be explained on the basis of focal calcification as determined by ultrasonic or angiographic images. Study of lesion pulsation by ultrasound imaging is proposed as a new noninvasive procedure for characterizing human carotid atherosclerosis.

Insulin kinetics in juvenile canine diabetics after glucose loading.

Glucose and insulin kinetics were studied in 4 juvenile canine diabetics and 6 healthy controls. Diabetic dogs were glucose intolerant with delayed insulin response after glucose challenge. Total insulin secretion was near that of the controls, but was inadequate when compared with corresponding plasma glucose concentrations.

Morphologic and immunocytochemical study of young dogs with diabetes mellitus associated with pancreatic islet hypoplasia.

In 11 dogs (7 males, 4 females; 10 purebred, 1 mixed breed), diagnosed as having diabetes mellitus before the age of 6 months, the pancreas was evaluated histologically; in 6, the pancreas also was examined by use of electron microscopy and/or immunocytochemical methods. Each dog was placed in 1 of 3 groups (A through C) on the basis of pancreatic histopathologic findings: Group A (n = 3)--no recognizable islets, but the pancreas in 2 dogs contained scattered endocrine cells detectable by use of immunoperoxidase staining or electron microscopy; Group B (n = 4)--no recognizable islets, but the pancreas had severe vacuolation of ducts and acini, as well as acinar atrophy; Group C (n = 4)--scant shrunken islets; 1 pancreas had reduced numbers of recognizable islets, hydropic beta-cell vacuolation attributable to glycogen deposition, and islet and nonislet endocrine cells in expected proportions. Insulitis was not observed in any pancreas, although scattered lymphocytes were seen in the pancreatic interstitial fibrous tissue of 3 dogs. Histologic pancreatic lesions in these young dogs were distinct from those of type-I (insulin-dependent) diabetes mellitus in human beings, as well as from those of diabetes mellitus in aged dogs, but were similar to those described in other young diabetic dogs. This uncommon syndrome is distinct from commonly recognized canine diabetes mellitus, on the basis of age of onset, predisposition for purebred dogs, lack of predisposing endocrinopathies or obesity, and pancreatic histologic features. The cause(s) is unknown, but is related to pancreatic endocrine hypoplasia and not to insulitis or to exocrine pancreatic inflammation. The term pancreatic islet hypoplasia is chosen as best describing this disorder.

Psychiatric training in primary care medicine residency programs. A national survey.

The authors conducted a national survey to investigate the current status of psychiatric training in primary care/internal medicine residencies. Fifty-four residency training directors completed and returned the survey. The survey results show that an average of 99 hours (69.5 hours clinical plus 29.8 hours didactics) is devoted to psychiatric training during the 3 years of primary care/internal medicine residency training. Responding residency training directors indicated that psychiatric training is important (an average of 7 out of 10 on a 10-point rating scale), and 63% of respondents indicated that more training in psychiatry is needed.

Abnormal insulin secretion in adult canines.

Insulin secretion after intravenous administration of glucose was studied in fourteen dogs, twelve of which were four years of age or older. Based on several characteristics of insulin secretion kinetics, normal and impaired insulin responses were defined in the experimental subjects. Among those, five exhibited a marked depression of the initial stage of insulin release which was followed by a stage of relative hyperinsulinemia. Similarities between canine and human insulin secretion patterns were noted, and the potential usefulness of the procedure for the early detection of canine diabetes mellitus discussed.

Body fat and fat distribution by anthropometry and the response to high-fat cholesterol-containing diet in monkeys.

Considerable variability exists among individuals in the response of plasma cholesterol to changes in dietary fat and cholesterol, and obesity is one variable reported to affect this response. This study was performed to determine the relationship between body fat and changes in plasma cholesterol in cynomolgus monkeys fed a high-fat cholesterol-containing diet for 12 months. The animals gained significant body weight (body mass index increased from 30.5 +/- 0.5 to 35.7 +/- 2.8 kg/m2) and skinfold parameters of body fat increased as well. Total cholesterol increased from 109 +/- 4 to 390 +/- 25 mg/dl (P < 0.001), and there were also significant increases in LDL- and HDL-cholesterol and triglyceride. While there was very little relationship between body fat and plasma lipids before the diet, after 12 months, there were significant negative correlations between total and LDL-cholesterol and anthropometric measures of body fat (r ranged from -0.37 to -0.55, P < 0.01). The correlations were not affected when the effects of baseline body mass index and serum cholesterol and total food intake were controlled by partial correlation analysis. In this sample of animals, the acquisition of greater body fat appeared to protect against rises in cholesterol in response to consumption of a high-fat cholesterol-containing diet.

Total serum cholesterol and plasma lipoprotein cholesterol concentrations in cord sera of newborns from hispanic mothers with gestational diabetes.

The objective of this research was to determine if gestational diabetes has an impact on the plasma lipoprotein profiles and/or cholesterol content of the plasma lipoproteins in newborns. Very low plus low density lipoproteins and high density lipoproteins in cord sera of newborns from gestational diabetic and non-diabetic mothers were isolated by heparin-affinity chromatography, and the cholesterol content in these plasma lipoprotein fractions were measured with an enzymatic assay. There were no significant differences in baby weights and total serum cholesterol levels between the two experimental groups. High density lipoprotein cholesterol levels (p less than 0.05) were significantly lower while very low plus low density lipoprotein cholesterol concentrations (p less than 0.05), very low plus low density lipoprotein cholesterol/high density lipoprotein cholesterol ratios (p less than 0.025), and total serum cholesterol/high density lipoprotein cholesterol ratios (p less than 0.025) were significantly elevated in newborns of diabetic mothers. These results suggest that gestational diabetes altered neonatal plasma lipoprotein metabolism.

Combined therapy of niacin, colestipol, and fat-controlled diet in men with coronary bypass. Effect on blood lipids and apolipoproteins.

The effects of colestipol (30 grams/day), niacin (7.3 grams/day), and diet on blood lipids and apolipoproteins after one year of therapy are reported. Men selected on the basis of previous coronary artery bypass surgery were randomly assigned to drug or control treatments in an angiographic study of atherosclerosis progression and regression. In 14 men, drugs and diet produced the following changes: Baseline total cholesterol 245 mg/dl, triglyceride 189 mg/dl, and LDL cholesterol 164 mg/dl were decreased by 73 mg/dl (29%), 83 mg/dl (41%) and 69 mg/dl (40%) respectively. Baseline HDL cholesterol, 44 mg/dl was increased 13 mg/dl (33%). Baseline apolipoprotein B, 124 mg/dl and apolipoprotein C-III (heparin precipitate) 5.6 mg/dl were decreased 40 mg/dl (31%) and 2.4 mg/dl (41%) respectively. All these changes are significant, p less than 0.01. Apolipoprotein A-I and apolipoprotein C-III (heparin supernate) were not significantly changed. In the controls, placebo and diet produced no significant decrease in blood lipid or lipoproteins, with the exception that baseline apolipoprotein B, 111 mg/dl increased 18 mg/dl (12%), p less than 0.05.

Work in progress: common carotid artery contours reconstructed in three dimensions from parallel ultrasonic images.

Three-dimensional sonograms of the common carotid artery were obtained using a device which takes images in parallel planes. Tests in phantoms simulating atherosclerotic vessels the same size as the common carotid artery indicated that the coefficient of variation of a single luminal measurement was 2-5%.

Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors.

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.

Autopsy calibration of carotid artery B-mode ultrasound imaging: effects of pressure on residual lumen size.

The accuracy of B-mode ultrasound (9 MHz) vascular imaging was studied on seven carotid arteries obtained at autopsy. Parallel cross-sectional images on five serial planes of each artery were compared with readings on corresponding sections of silicone rubber replicas of the vessel lumens and with histologic sections. A close correlation between ultrasound and cast measurements was observed (r = 0.88, p less than 0.01), and both corresponded well with histologic measurements. Longitudinal ultrasound views of the arteries were employed to determine changes of normal vessel diameter (maximum lumen diameter) and residual lumen diameter with increasing arterial pressure. In the specimens studied, compression of lesions occurred in addition to circumferential vessel enlargement, and the rate of compression of lesions exceeded that of circumferential vessel diameter enlargement.