Blood platelets from eight patients with hyperbetalipoproteinemia (type II) were more reactive to aggregating agents in vitro than those of 13 type IV patients or 12 normal subjects. Platelets of two patients with abeta-lipoproteinemia were also slightly hyperreactive in comparison with normal platelets. However, in one patient with Tangier disease the platelets were distinctly hyporeactive to aggregating agents. Total platelet phospholipid concentration (PL) was elevated in the four groups of patients studied but was highest in the platelets of type IV patients. Platelet-free cholesterol (FC) was significantly higher than normal in all of the dyslipoproteinemias studied. The FC was highest in the two patients with abetalipoproteinemia. The FC/PL molar ratio was normal in all but the abeta-lipoproteinemic patients, in whom it was markedly elevated. Therefore, there is no apparent correlation between FC/PL molar ratio and platelet behavior in vitro. Analysis of individual platelet phospholipids in the four patient groups showed that platelets in Tangier disease had very low concentrations of lysolecithin and phosphatidylinositol (PI) in comparison with normal platelets and the other disease states. Our findings suggest that lysolecithin and phosphatidylinositol may be involved in the structure or function of the sites which modulate platelet response to aggregating agents.

Abetalipoproteinemia↗

PubMed1979

Clofibrate and atherosclerosis.

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Arteriosclerosis↗

PubMed1979

Low density lipoprotein metabolism in type IV and type V hyperlipoproteinemia.

Low density lipoproteins (LDL) are thought to arise largely from degradation of triglyceride-rich very-low-density lipoproteins (VLDL). LDL kinetics in patients with Type IV and Type V hyperlipoproteinmia were studied and compared with normal subjects. LDL labeled in the protein moiety with 125I was used as a tracer. There was no significant difference in LDL turnover between the three groups, suggesting that a catabolic defect in VLDL degradation to LDL may exist in both Type IV and Type V hyperlipoproteinemia.

Adult↗

PubMed1979

The natural history and surgical significance of hyperlipemic abdominal crisis.

Although it is widely known that patients with severe hyperlipemia may have pancreatitis, it is not generally appreciated that such patients may have recurrent abdominal pain of variable character and intensity not due to pancreatitis. Review of 35 patients followed in our clinic for 1--11 years showed that 54% had recurrent abdominal pain, while only 29% had pancreatitis. Although mild pain occurred frequently with plasma triglycerides in the 2000--5000 mg/dl range, triglycerides over 6000 mg/dl were often associated with severe pain and physical findings which necessitated hospitalization, often led to the misdiagnosis of pancreatitis and other intra-abdominal catastrophes and resulted in multiple unnecessary diagnostic studies and operations. When recognized, the pain subsided within 48 hours upon cessation of oral intake and treatment with intravenous electrolyte solutions. Furthermore, effective treatment of the hyperlipemia prevented both the attacks of severe pain and the pancreatitis which otherwise occurred (or recurred) in a significant fraction of the patients. These data confirm the existence of hyperlipemic abdominal crisis as a distinct entity and testify to the importance of recognizing this syndrome in order to avoid the occurrence of acute pancreatitis and the performance of unnecessary and potentially harmful surgery.

Abdomen↗

PubMed1979

Immunofluorescence studies of apolipoprotein B in intestinal mucosa. Absence in abetalipoproteinemia.

During fat absorption, active synthesis of cholesterol, phospholipids, and specific apolipoproteins are required for chylomicron formation and secretion. In the inherited disease abetalipoproteinema, chylomicrons cannot be made in response to fat feeding, and they as well as low and very low density lipoproteins are completely absent from plasma. The genetic defect in the disease is presumed to be an inability to synthesize apolipoprotein B, the apoprotein common to all the above lipoprotein classes, but such a defect has not been directly demonstrated. With peroral intestinal biopsies and immunofluorescence and intracellular localization of apolipoprotein B within jejunal epithelial cells of five normal subjects and have shown that its content increases markedly after fat feeding. In two patients with abetalipoproteinemia no apolipoprotein B was seen by immunofluorescence techniques in the jejunal mucosa in the fasting state or after a fatty meal. Intestinal synthesis of apolipoprotein B appears not to occur in abetalipoproteinemia.

Abetalipoproteinemia↗

PubMed1978

Apoprotein A-I synthesis in normal intestinal mucosa and in Tangier disease.

To determine whether human small intestine synthesizes apoA-I, the major apoprotein of plasma high-density lipoproteins, we used immunofluorescence technics and monospecific antiserums to visualize apoA-I within intestinal epithelial cells from four normal subjects and one patient with Tangier disease. Biopsies from all subjects during fasting showed limited fluorescence. After lipid feeding intracellular apoA-I markedly increased in both normal subjects and the patient. During alimentary lipemia, mean plasma apoA-I levels (milligrams per deciliter) increased in four normal subjects from 161 +/- 12 (+/- S.E.M.) to 180 +/- 15 (P less than 0.05) and in the patient from 1.9 to 6.8. Normal plasma chylomicrons contained apoB, apoE and the C peptides but not apoA-I. The patient's chylomicrons contained ap0A-I. Normal and Tangier-disease intestinal-mucosa cells increase their content of apoA-I during chylomicron formation and subsequently contribute to plasma apoA-I levels. The low levels of apoA-I in Tangier disease are not due to a failure of intestinal synthesis but might be due to abnormal metabolism of chylomicron apoproteins.

Apolipoproteins↗

PubMed1978

Hypercholesterolemia and platelets.

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Arachidonic Acids↗

PubMed1978

Effect of intessive plasmapheresis on the plasma cholesterol concentration with familial hypercholesterolemia.

Plasmapheresis was studied as a means of reducing the serum cholesterol concentration in 3 hypercholesterolemic patients who each underwent courses of intensive plasmapheresis with removal of 250--500 ml of plasma each day for 5--9 days. In one homozygous Type II patient, the serum cholesterol concentration decreased from 609 +/- 45 mg/100 ml (mean +/- SEM) to 365 +/- 17 mg/100 ml (40% decrease, P less than 0.05) with two different courses of plasmapheresis. In the two other patients with non-homozygous hyperbetalipoproteinemia the serum cholesterol concentration decreased from 289 +/- 27 mg/100 ml to 205 +/- 19 mg/100 ml (29% decrease, p less than 0.05). After cessation of treatment, the cholesterol concentration returned to pre-treatment levels in 10--13 days in the homozygous patient and 7 days in one non-homozygous hyperbetalipoproteinemic patient; clofibrate (2 g/day) in this patient was associated with a smaller reduction of the cholesterol concentration with plasmapheresis and an increased rate of return of pre-treatment levels after plasmapheresis was stopped. Sustained plasmapheresis for 6 days in the other non-homozygous hyperbetalipoproteinemic patient resulted in a new approximate "steady state" with a serum cholesterol concentration of 176--199 mg/100 ml compared with a pre-plasmapheresis value of 227 mg/100 ml. The response of the plasma cholesterol levels to plasmapheresis was subjected to kinetic analysis based on a current model of the regulation of lipoprotein metabolism.

Adolescent↗

PubMed1978

The bruit of carotid stenosis versus radiated basal heart murmurs. Differentiation by phonoangiography.

Phonoangiography, quantitative analysis of arterial bruits, has been shown to provide accurate noninvasive diagnosis of uncomplicated carotid arterial stenosis, but had not been tested where cervical bruits from other sources were present. In this study, 27 carotid bruits in 15 consecutive patients with carotid bruits and basal heart murmurs were analyzed by phonoangiography. Tape recordings were made over the base of the heart and along the course of the carotid arteries in the neck; spectral analysis was performed as previously described. The spectral shape of the basal heart murmurs was recognizable and amplitude decreased with distance from the heart, althouth a secondary, lower amplitude, maximum often occurred over the carotid bifurcation. Intrinsic carotid bruits, by contrast, were always maximal over the bifurcation, and although they radiated both proximally and distally, were not detectable over the chest wall. In quantitative terms, the correct diagnosis as to the presence and extent of carotid stenosis was made in 25 of 27 cases (92%) despite the presence of a radiated murmur. Phonoangiography is capable of accurate differentiation of radiated murmurs from intrinsic carotid bruits and of quantitation of the latter even in the presence of radiated sounds.

Carotid Artery Diseases↗

PubMed1978

Interaction of collagen with the lipids of tendon xanthomata.

To determine the physical state of lipids in tendon xanthomata, six specimens surgically removed from three patients with familial hypercholesterolemia were studied by microscopy, calorimetry, and x-ray diffraction. The major constituents of the xanthomata were lipid (33% of dry weight) and collagen (24% of dry weight). The principal lipids were cholesterol ester and cholesterol. Light microscopy and thin-section electron microscopy showed occasional clusters of foam cells separated by masses of extracellular collagen. Polarized light microscopy of fresh, minced tissue showed rare droplets of free cholesterol ester. When heated, the tissue shrank abruptly at approximately equal to 70 degrees C and, consequently, a large amount of cholesterol ester was released. Scanning calorimetry of fresh pieces of xanthoma showed a single, broad, reversible liquid crystalline transition of cholesterol ester with peak temperature from 32 to 38 degrees C. The enthalpy (0971 +/- 0.07 cal/g) was reduced compared with the isolated cholesterol ester from each xanthoma (1.1+/-0.01 cal/g). There was a large irreversible collagen denaturation endotherm (peak temperature = 67 degrees C; enthalpy 9.9 cal/g collagen) that corresponded to the tissue shrinkage noted by microscopy. After the collagen denaturation, the sample displayed double-peaked reversible liquid crystalline transitions of cholesterol ester, of enthalpy 1.18 +/- 0.1 cal/g, that were identical to transitions of isolated cholesterol ester. Fibers dissected fron xanthomata were examined by X-ray diffraction at temperatures below and above the cholesterol ester transition. At 20 degrees C there was a weakly oriented equatorial reflection of Bragg spacing 36A, which corresponded to the smectic phase of cholesterol ester, and a series of oriented collagen reflections. At 42 degrees C the cholesterol ester reflection disappeared. Stretched fibers examined at 10 degrees C showed good orientation of collagen and cholesterol ester reflections, and in addition, meridional spacings which indicated oriented crystallization of cholesterol ester. These studies suggest that a major component of tendon xanthomata is extracellular cholesterol ester which displays altered melting and molecular orientation as a result of an interaction with collagen. At xanthoma temperatures, the cholesterol ester is in a smectic liquid crystalline state, probably layered between collagen fibrils, with the long axis of the cholesterolester molecules perpendicular to the axis of the collagen fiber. Such collagen-cholesterol ester interactions may favor the extracellular deposition of cholesterol ester derived either from intracellular sources or directly from plasma lipoproteins.

Adult↗

PubMed1978

Characterization of normal and abnormal pulmonary surface by reflected ultrasound.

The use of reflected ultrasound in the diagnosis of pulmonary disease has been limited due to the strong reflection and high absorption of acoustic energy by alveoli containing air. Our study reports the ultrasonic characteristics of normal and diseased pulmonary surface. Two measurements, the coefficient of pulmonary reflection and the tissue frequency signature, were studied with specially calibrated instuments. The coefficient of pulmonary reflection in 23 normal subjects was - 19.6 +/- 0.1 dB at 5.5 MHz. In ten patients with documented pulmonary emboli, the coefficient of pulmonary reflection was -47.4 +/- 0.1 dB, significantly less than normal (P less than 0.1). The tissue frequency signature in 18 normal subjects was specular at higher and nonspecular at lower frequencies, with a typical dip at 5.2 MHz. In patients with chronic obstructive pulmonary disease, the tissue frequency signature was flat, and the typical dip was absent. In patients with pulmonary emboli, the characteristic shape of the tissue frequency signature was preserved, but there was a generalized loss of magnitude of the reflection. Thus, our preliminary data indicate that reflected ultrasound provides a noninvasive method for differentiating normal from diseased pulmonary surfaces.

Animals↗

PubMed1978

Nitroglycerin for neurosurgery.

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Animals↗