The modernization of Asia. Implications for coronary heart disease. Council on Arteriosclerosis of the International Society and Federation of Cardiology.
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Asia↗
Biomedical subjects
A Postiglione
Publications and source records attributed to A Postiglione.
Different thallium-201 single-photon emission tomographic patterns in benign and aggressive meningiomas.
To evaluate the possibility of preoperatively obtaining an index of aggressiveness for intracranial meningiomas, we prospectively studied 22 patients with computed tomographic or magnetic resonance imaging evidence of meningeal tumour, using single-photon emission tomography (SPET) of the brain and thallium-201 (201Tl). On a brain-dedicated SPET scanner, a rapid acquisition protocol with early, short scans was started simultaneously with the intravenous administration of 111 MBq 201Tl, covering the initial intratumoral distribution of the tracer. Twenty minutes post injection, a delayed SPET scan was also obtained. On the reconstructed and attenuation-corrected images we calculated the 201Tl concentration in tumour and normal contralateral brain tissue, and compared intratumoral tracer concentration in the initial and the final part of the rapid acquisition protocol. Benign and malignant meningiomas were classified as such based on histological examination. In malignant lesions, the ratio of the 201Tl concentration at 2-4 min post injection to that at 14-16 min was found to be significantly higher than in non-aggressive neoplasms (mean+/-1 SD: 1.14+/-0.31 and 0.56+/-0.13, respectively, P <0.01). Conversely, in the delayed scan, most lesions showed high tracer concentration, and the two groups could not be distinguished. In addition, three recurrent meningiomas displayed the same imaging behaviour as the malignant group, i.e. had similar 201Tl concentration values at 2-4 and at 14-16 min. Our findings suggest that the comparative assessment of intratumoral 201Tl concentration at 2-4 and at 14-16 min post injection could provide a fast, simple method to differentiate preoperatively intracranial meningiomas with different biological behaviour.
Female↗
Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses.
Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABAA receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (Vd) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured Vd in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex Vd was significantly (P<0.02) reduced: temporal Vd averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal Vd averaged 71 ml/ml in normals and 48 ml/ml in AD. These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlate closely with the mental deterioration in AD.
Alzheimer Disease↗
Plasma lipoprotein(a) levels in subjects attending a metabolic ward. Discrimination between individuals with and without a history of ischemic stroke.
In this cross-sectional study we compared the abilities of lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) to discriminate between individuals with and without a history of stroke from among subjects in a metabolic ward. A total of 210 subjects (108 men and 102 women; mean age, 63.8 years; range, 31 to 86 years) provided plasma and DNA samples for the study. Of these, 51 men and 50 women had a history of ischemic stroke. The 109 subjects without a history of stroke were compared with those with such a history for major risk factors for ischemic events. Mean plasma TPA and PAI-1 levels significantly (P < .001) discriminated among subjects younger than 70 years with a history of stroke. The mean plasma Lp(a) level of stroke subjects (21.9 mg/dL) did not differ significantly from that of control subjects (15.2 mg/dL). However, among individuals < 70 years old, Lp(a) plasma levels > 50 mg/dL were more common among stroke patients (8 with versus 1 without, P < .01 by chi 2 test). A molecular variation in the 5' flanking region of the apo(a) gene that has been related to elevated Lp(a) plasma levels (G/A-914) was not strongly correlated with circulating levels of Lp(a), nor did Lp(a) levels correlate with a polymorphism of the apo(a) gene (G/A-21), which is strongly linked (P < .001) to the G/A-914 variation. In this setting, the relation between Lp(a) and cerebral ischemia appears to be limited to individuals below 70 years with elevated (> 50 mg/dL) plasma levels of the lipoprotein.
Adult↗
[LDL oxidation in homozygous familial hypercholesterolemia: effects of selective LDL-apheresis treatment].
Homozygous familial hypercholesterolemia (HFH) results from a mutation affecting both the structure and function of a cell surface receptor that removes low density lipoproteins (LDL) from plasma. The disorder is characterized by autosomal dominant inheritance, a lifelong elevation in the concentration of LDL-bound cholesterol in blood and by cholesterol deposits that form xanthomas and early coronary artery disease. HFH patients, as a result of the increased levels and prolonged residence time of LDL in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall causing premature atherosclerosis. Selective LDL-apheresis (LA) on dextran/sulphate cellulose columns is the best therapy reducing mortality of these patients. We previously showed that prolonged lifelong enhanced LDL oxidation in HFH. LDL undergo oxidation before being taken up by macrophages then transformed into foam cells. At the present time, the relevance of the in vitro macrophages studies to the accumulation of cholesterol esters in scavenger cells of HFH patients is not yet established. The aim of this study was to investigate LDL oxidation, induced by xanthine (2 mM)+xanthine oxidase (100 mU), and cholesterol esterification in macrophages, in 8 HFH patients before and after LA. LDL peroxidation by conjugated-diene absorbance showed an increased resistance against oxidation after LA: lag time 129 +/- 25 vs 112 +/- 27 min, p < 0.05; diene production 9.1 +/- 2.1 vs 13.9 +/- 2.5 nM/min/mg LDL, p < 0.01. Peroxidation was also evaluated from lipid peroxides (158 +/- 34 vs 57 +/- 18 nM/mg protein after LA, p < 0.05) and malonyldialdehyde (38 +/- 12 vs 27 +/- 8 nM/mg protein after LA, p < 0.05) content. When oxidized LDL was run on polyacrylamide gel extensive apo-B100 fragmentation was observed in LDL before LA, vs a less fragmentation after LA. A similar reduction was obtained in LDL agarose mobility after LA (1.7 +/- 0.2 vs 2.5 +/- 0.2, p < 0.05). Cholesterol esterification in mouse peritoneal macrophages was also decreased after LA (8.5 +/- 1.8 vs 14.6 +/- 2.7 nM/mg cell protein/12 hours, p < 0.05). Vitamin E content of LDL (mg/g protein) was increased after LA (4.44 +/- 1.0 vs 3.9 +/- 1.2, p < 0.05). Thus, selective LA, not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation and decreased high cholesterol esterification in macrophages. The prevention of these mechanisms by LA contributes actively to retard atherogenesis in HFH patients.
Analysis of Variance↗
Dietary intake, plasma levels of antioxidant vitamins, and oxidative stress in relation to coronary artery disease in elderly subjects.
The prevalence of coronary artery disease (CAD) in the urban population of India is similar to that in developed countries; Indian immigrants in industrialized countries have the highest prevalence of CAD. This is a cross-sectional survey within a random sample of a single urban setting in India. The relation between risk of CAD and plasma levels of vitamins A, C, E, and beta-carotene was examined in 72 of 595 elderly subjects (12.1%) with CAD (aged 50 to 84 years). Plasma levels of vitamins A, C, E, and beta-carotene were significantly related to risk of CAD. Smoking (n = 145) and diabetes (n = 70) were the confounding factors. Lipid peroxides were higher in patients with CAD and diabetes, and in those who smoked. The inverse relation between CAD and low plasma vitamin C was substantially reduced after adjustment for smoking and diabetes. Vitamin A and E levels remained independently and inversely related to the risk of CAD after adjustment for age, smoking, diabetes, blood pressure, blood lipoproteins, and relative weight and body mass index. The adjusted odds ratios for CAD between the lowest and highest quintiles of vitamin E levels were 2.53 (95% confidence interval [CI] 1.11 to 5.31), vitamin C, 2.21 (95% CI 1.12 to 3.15), and beta-carotene, 1.72 (95% CI 0.88 to 3.62). The fatty acid composition of the diet, blood lipid levels, central obesity (waist-hip ratio), smoking habits, blood pressure, and plasma insulin levels do not appear to account for high rates of CAD among elderly Indians.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Cu/Zn superoxide dismutase in patients with non-familial Alzheimer's disease.
Chromosome 21 contains genes whose altered expression has long been associated with Down's syndrome and whose altered structure with some cases of Alzheimer's disease (AD). The gene for the Cu/Zn superoxide dismutase enzyme (SOD-1), a key enzyme in the metabolism of oxygen free radicals, is located on the distal portion of chromosome 21. Due to the triplication of the SOD-1 gene, patients with Down's syndrome have an almost 50% increase in their SOD activity. On the other hand, almost 25% of the patients with Down's syndrome over 40 years of age develop progressive dementia, with clinical symptoms of AD. Therefore, we decided to evaluate whether abnormalities in the production of free radicals could be detected in blood cells from AD patients, and whether they correlated with molecular variations in the Cu/Zn SOD-1 gene. Superoxide anion production was evaluated spectrophotometrically in suspensions of monocytes from 9 sporadic AD patients, and from 9 aged-matched apparently normal controls. After stimulation with increasing concentrations of n-formyl-methionyl-leucyl-phenylalanine (fMLP) or Ca ionophore A23187, monocyte free radical generation was quantitatively and qualitatively normal. Furthermore, restriction fragment length polymorphism (RFLP) analysis of leukocyte DNA digested with a variety of enzymes, gave comparable results in patients and controls. Our data support the possibility that in addition to the generation of free radicals, other directions should be explored to elucidate the mechanisms of dementia in AD.
Aged↗
Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia.
Patients with homozygous familial hypercholesterolemia (FH), as a result of the increased levels and prolonged residence time of low density lipoprotein (LDL) in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall, causing premature atherosclerosis. This phenomenon may enhance per se the physiological degradation of both protein and lipid component of LDL, which be more susceptible to oxidative damage induced by oxygen radicals. It is well known that LDL may undergo oxidative modification before being taken up by macrophages which are then transformed into foam cells. It has been suggested that platelet-activating factor (PAF) may play an important role in atherogenesis and PAF catabolism is known to be mediated by serum acetylhydrolase, an enzyme that is normally associated with LDL. Thus, the present study was designed to investigate the structural properties of LDL, including acetylhydrolase activity, in homozygous FH as compared to normolipidemic subjects before and after xanthine/xanthine oxidase-mediated oxidation. We studied 8 homozygous FH patients matched with 8 normolipidemic volunteers. Lipids of LDL fraction were extracted and verified by thin layer chromatography (TLC) analysis. Fatty acids were methylated and injected into a gas chromatograph/mass spectrometer. Vitamin E in LDL was determined by high performance liquid chromatography (HPLC). As an index of susceptibility of LDL to oxidative modifications, the formation of lipid-conjugated dienes was continuously monitored at 234 nm. Lipid peroxidation was also evaluated from the amount of both lipid peroxides (LPO) and malonyldialdehyde (MDA) content. Apolipoprotein (apo) B-100 on LDL was carried on polyacrylamide and agarose gel electrophoresis. In the homozygous FH patients, the relative content of cholesteryl ester was slightly increased. Interestingly, the relative amount of arachidonic acid (20:4) was constantly increased in each lipid fraction in homozygous FH patients. The amount of vitamin E was not significantly different in the patient group from that in the control group. However, LDL from patients carried lower levels of vitamin E (nmol/mg LDL) than controls (2.7 +/- 0.4 vs. 2.9 +/- 0.3 P = NS). The results shows that lag time (min) was decreased (82 +/- 19 vs. 111 +/- 21; P < 0.05) and the maximal rate of diene production and total diene production was increased in homozygous FH patients. Mean levels of MDA were similar in both groups before oxidation, but levels after initiation of oxidation were significantly higher in the patient group. In contrast, mean levels of LPO were already higher in patients before oxidation (58 vs. 27 nmol/mg of protein; P < 0.05), and after initiation of oxidation were also significantly higher at each time points. When oxidized LDL was run on a polyacrylamide gel, an extensive apo B-100 fragmentation replaced by lower molecular mass fragments ranging from 45,000 to 205,000 m.wt., was observed only in LDL from homozygotes. Relative LDL agarose gel mobility shows that LDL from patients migrated higher than LDL of controls. Finally acetylhydrolase activity associated with LDL in patients was significantly reduced as compared to controls. Thus, in homozygous FH patients, LDL appeared more susceptible to oxidation in vitro; the indices for LDL oxidizability were all significantly different from those of controls. This phenomenon might be due to prolonged residence time of LDL in these patients, as suggested from high basal LPO levels and lower vitamin E levels carried by LDL. This hypothesis may explain together with the high content of arachidonic acid, the enhanced susceptibility of LDL from homozygous FH patients to oxidative damage.
Apolipoprotein B-100↗
Epidemiological study of coronary artery disease and its risk factors in an elderly urban population of north India.
OBJECTIVE: In view of the rapid increase in the prevalence of coronary artery disease (CAD) in developing countries, our aim was to determine the prevalence of CAD and its risk factors and lifestyle factors in an elderly population from north India. METHODS: A random sample of 595 elderly subjects between 50 to 84 years of age was obtained from the urban population of Moradabad. The response rate was 90.1%. The survey methods included a questionnaire containing information on 7-day food intake, other lifestyle factors, Rose questionnaire for diagnosis of angina pectoris, a standard 12-lead electrocardiogram, blood pressure measurements and blood examination. RESULTS: The total prevalence of CAD based on clinical history and electrocardiogram was 121/1000 (95% CI 72 to 165). The prevalence rate was slightly higher in males (130/1000) than in females (110/1000). The prevalence of CAD based on the Rose questionnaire was 57/1000 and based on electrocardiogram in 561 asymptomatic subjects was 67/1000. CAD was significantly higher in the elderly (65 to 84 years) group than in the middle-aged (50 to 64 years) group (168 vs. 97 per 1000), respectively. While the prevalence of hypertension was significantly higher in the elderly than middle-aged group respectively (214 vs. 168 per 1000), the prevalence of central obesity was significantly higher in the middle-aged than elderly group (674 vs. 632 per 1000). Other risk factors including smoking were comparable in the two subgroups. Prevalence of major risk factors and central obesity were significantly higher among patients with CAD than in the rest of the subjects. Prevalence of CAD was significantly higher in the middle and higher socio-economic groups compared to the lower income group. These higher income groups were also eating significantly higher amounts of visible fat and had a higher prevalence of physical inactivity (93.3%) compared to the lower income group. CONCLUSIONS: CAD and its risk factors such as hypertension, hypercholesterolemia, diabetes and central obesity are of sufficient magnitude in the elderly population of India to be a major public health problem. The findings also indicate that CAD is more commonly associated with middle and higher socio-economic status which may be due to greater consumption of dietary fat and more sedentariness compared to lower socioeconomic groups.
Aged↗
Hyperlipidaemia and atherosclerotic cerebrovascular disease.
Controversies exist concerning the role of hypercholesterolaemia as a risk factor for nonhaemorrhagic stroke because intracranial arteries seem to be more resistant than coronary arteries to cholesterol-induced endothelial damage. Only very high levels of serum cholesterol seem to be a significant risk factor. It is possible that coronary heart disease may occur earlier in life than cerebrovascular atherosclerosis, and it could then become the cause of stroke. In our view, the causal relationship between very low levels of serum cholesterol and haemorrhagic stroke is unlikely, and cholesterol-lowering treatment appears to be safe. New studies should consider the particular metabolic aspects of intracranial arteries and the independent role of lipoprotein (a), apolipoprotein E phenotypes and other molecular and genetic mechanisms involved in atherosclerotic cerebrovascular disease.
Arteriosclerosis↗
Carotid diameter and blood flow velocities in cerebral circulation in hypertensive patients.
BACKGROUND AND PURPOSE: The recent development of noninvasive techniques for the evaluation of the carotid arteries has focused attention on the study of arterial wall thickness to identify early lesions of vessels in patients at high risk for atherosclerosis, such as those with hypercholesterolemia, diabetes mellitus, and hypertension. METHODS: In a sample of 70 hypertensive patients without clinical evidence of target organ damage, we showed a thickening of the intimal plus medial layers compared with age- and sex-matched normotensive control subjects. In this sample we also studied the diameter of the carotid arteries by ultrasound imaging, and we studied flow velocities in common carotid, internal carotid, and middle cerebral arteries by Doppler technique. Pulsatility and resistance indexes were calculated. RESULTS: Absolute values of the carotid diameter were similar in the two groups (6.3 +/- 0.7 versus 6.0 +/- 0.8 mm); however, the ratio of diameter to blood pressure was significantly reduced in hypertensive compared with normotensive subjects (5.3 +/- 0.7 versus 6.5 +/- 0.8; P < .001 for mean blood pressure). Parietal stress was increased in the hypertensive subgroup and significantly correlated with arterial diameter in the normotensive group but not in the hypertensive group. No significant differences between the two groups were observed in blood flow velocities, with the exception of a slight significant increase of mean velocity in the internal carotid artery in hypertensive patients (37.5 +/- 9.1 versus 32.7 +/- 3.0 cm/s; P < .02). CONCLUSIONS: These results indicate that in addition to the degenerative changes of the common carotid wall, the diameter of the carotid artery and the relation to parietal stress show an early impairment in patients with uncomplicated hypertension.
Blood Flow Velocity↗
Effect of adenosine on cerebral blood flow as evaluated by single-photon emission computed tomography in normal subjects and in patients with occlusive carotid disease. A comparison with acetazolamide.
BACKGROUND AND PURPOSE: Acetazolamide is commonly used with single-photon CT to assess the cerebrovascular reserve in patients with internal carotid artery stenosis or occlusion. In this study we wanted to evaluate the effects of adenosine, a well-known vasodilatatory compound with a short biological half-life, on brain circulation in humans and compare the results with those of acetazolamide. METHODS: Acetazolamide (1 g) and adenosine (140 micrograms/kg per minute) were injected intravenously on different days in 6 normal subjects and 6 patients: 4 with unilateral stenosis, 1 with bilateral stenosis, and 1 with complete occlusion of the internal carotid artery. Changes in regional cerebral blood flow relative to that of the cerebellum (cortico/cerebellar ratios) from resting conditions were evaluated by 99mTc-hexamethylpropyleneamine oxime and single-photon emission CT. RESULTS: The measured blood flow ratios increased significantly in the normal group 20 minutes after acetazolamide injection in several cortical and subcortical regions, as well as at the 4th minute of a 6-minute adenosine infusion. Regional cerebral blood flow ratio values were higher after adenosine than after acetazolamide in both cortical (frontal and parietal) and subcortical (thalamus and basal ganglia) regions. In 4 of the 6 patients the side-to-side asymmetry increased from the basal resting condition after the injection of acetazolamide and even more so after the injection of adenosine. CONCLUSIONS: Adenosine infusion causes vasodilation of cerebral arteries and can be used for the investigation of cerebrovascular perfusion capacity in patients with carotid occlusive disease. One advantage in the use of adenosine over acetazolamide is the possibility of interrupting the test with reversal of clinical symptoms or patient discomfort within a few minutes.
Acetazolamide↗
Cerebral blood flow in patients with dementia of Alzheimer's type.
In the normal brain as well as in Alzheimer's disease (AD), regional cerebral blood flow (CBF) is coupled to metabolic demand and, therefore, changes in CBF reflect variations in neuronal metabolism. The use of radionuclide techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), provides an accurate assessment of regional functional activity, i.e., CBF and metabolism, and could be very helpful for the differential diagnosis of AD. This disease is characterized by a decrease in global CBF and metabolism. When found, a symmetric bi-parieto-temporal CBF reduction is highly diagnostic for AD, despite the fact that a similar CBF pattern could also be observed in other types of dementia. Many AD patients with parieto-temporal flow reduction also have a diffuse flow reduction in the frontal cortical areas, particularly in advanced stages of the disease. Lateral CBF asymmetry is also very frequent; speech disorders are highly characteristic of left-sided flow reduction, while visuospatial apraxia is dominating in the right-sided cases. In advanced and severe cases of AD, CBF and metabolism tend to be more uniformly reduced throughout the cortex, sparing only the primary visual and sensory-motor cortices. PET and SPECT measurement of brain perfusion and metabolism has added a new dimension to the knowledge of dementia disorders, with a better differential diagnosis between AD and other forms of dementia. The correlation with neuropsychological data has also given new insight into the disease.
Aging↗
Fatal septicaemia caused by Aeromonas hydrophila in a patient with cirrhosis.
In this case report from Italy we describe a fatal infection caused by A. hydrophila in a 39 yr old cirrhotic patient. This pathogen was isolated as a pure single culture from the patient's blood sample. The patient died on the second day of hospitalization from overwhelming sepsis. The A. hydrophila isolate was tested for different potential virulence properties, such as invasiveness, adherence, exotoxins production, presence of fimbriae and for the patterns of resistance to a variety of antimicrobial agents. Although, the Aeromonas species are infrequently reported as a cause of human infections, the present case study confirms the capability of these pathogens to induce serious human infections.
Adult↗
Effect of acetyl-L-carnitine treatment on brain adenylate cyclase activity in young and aged rats.
The aim of the present study has been to evaluate the effect of acetyl-L-carnitine (ALCAR) on brain adenylate cyclase (AC) activity in adult and aged rats. In in vitro studies, ALCAR (1, 10 and 100 microM) did not exert any effect on frontal cortex basal AC activity. Acute and subchronic administrations of ALCAR were carried out in 4- and 25-month-old male Fisher rats and AC activity was determined in rat frontal cortex under both basal and stimulated conditions. The acute treatment of young rats with ALCAR (100 and 500 mg/kg s.c.) did not affect AC activity, whereas the subchronic administration of 250 mg/kg s.c. ALCAR enhanced the stimulation of AC by carbamylcholine (CCh), norepinephrine (NE) and dopamine (DA), without affecting the basal AC activity. Basal AC activity in old rats was lower than in young rats and was not modified by acute and subchronic ALCAR administration. Moreover, the response of the enzyme to CCh, NE and DA was potentiated by the subchronic administration of ALCAR. The concentration-response curve of CCh stimulation of AC activity in ALCAR-treated rats is shifted to the left in both young and aged rats. We conclude that ALCAR, subchronically administered, is able to enhance receptor-stimulated AC response in frontal cortex of both young and aged rats.
Acetylcarnitine↗
Serum lipoprotein fatty acid profile in hereditary ataxias.
We investigated the serum fatty acid profiles of cholesterol esters, phospholipids and triglycerides in 24 patients with Friedreich's disease and 16 patients with other forms of spinocerebellar degeneration. In 8 patients with Friedreich's disease we also analyzed the fatty acid profile of the lipoprotein fractions. We found no major differences in fatty acid profiles between ataxic patients and sex and age-matched controls; in particular there was no decrease of linoleic acid in Friedreich's disease. The level of linoleic acid in serum cholesterol esters decreased with increasing disability of patients.
Adolescent↗
Functionally abnormal monocytes in hypercholesterolemia.
We investigated some functions of monocytes from 20 type IIa hypercholesterolemic (HC) and five homozygous familial hypercholesterolemic (FH) patients. Monocytes from the HC patients contained as much cholesterol and formed as much thromboxane B2 in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) or calcium ionophore A23187 as those from normal individuals. In contrast, the generation of prostaglandin E2 and 6-ketoprostaglandin F1 alpha in response to these agonists was 1.5-3 times normal, and that of leukotriene B4 was 40-60% of the normal value (p < 0.05 for all). Studies in which the combination of fMLP or A23187 with sodium arachidonate were employed suggested that these abnormalities were independent of the availability of the endogenous substrate for the lipoxygenase or cyclooxygenase enzymes. Quantitatively and qualitatively comparable abnormalities were found in monocytes from the five FH patients, and these were little affected when the patients' plasma cholesterol levels were almost normalized by low density lipoprotein apheresis. In keeping with the abnormalities in the eicosanoid metabolism, monocytes from HC patients exhibited a defective ability (p < 0.05) to generate O2-, the extent of which was correlated with the impaired formation of leukotriene B4. On the other hand, adhesion studies indicated that patients' cells exhibited an abnormally high ability to adhere to glass (p < 0.01). These data indicate the presence of functionally abnormal monocytes in hypercholesterolemia and suggest a direction to be followed to understand the importance of such cells in the premature atherosclerosis that occurs in these patients.
Adolescent↗
Cerebral blood flow velocity and systemic vascular resistance after acute reduction of low-density lipoprotein in familial hypercholesterolemia.
BACKGROUND AND PURPOSE: Low-density lipoprotein apheresis is currently used for the treatment of familial hypercholesterolemia, an inherited disorder of metabolism associated with premature development of cardiovascular disease. We wanted to evaluate cerebral blood flow velocity, cardiac output, and systemic vascular resistance in patients with familial hypercholesterolemia before and after low-density lipoprotein apheresis. METHODS: Ten patients (age range, 14 to 46 years; 4 males, 6 females) with familial hypercholesterolemia (8 homozygotes, 2 heterozygotes) and 10 healthy control subjects of comparable age and sex distribution participated in the study. Low-density lipoprotein apheresis by dextran sulfate was performed in 8 patients (7 homozygotes, 1 heterozygote). Six patients (4 homozygotes, 2 heterozygotes) underwent a procedure of extracorporeal erythrocyte filtration with the same extracorporeal volume as for low-density lipoprotein apheresis, but with the exclusion of the passage of plasma through the dextran sulfate column. Cerebral blood flow velocity (transcranial Doppler), cardiac output, and systemic vascular resistance (electric bioimpedance cardiography) were determined by noninvasive techniques before and 1 day and 7 days after low-density lipoprotein apheresis or extracorporeal erythrocyte filtration. Plasma and blood viscosities were measured at the same time. RESULTS: Before apheresis, mean and diastolic cerebral flow velocities were abnormally low in hypercholesterolemic patients (P < .01 and P < .02 vs healthy control subjects, respectively). After apheresis, low-density lipoprotein cholesterol was lowered by 40% to 60% from baseline, and cerebral blood flow velocities (mean, systolic, and diastolic velocities) were increased (P < .01). Cardiac output, systemic vascular resistance, and viscosity values were not significantly modified. Extracorporeal erythrocyte filtration (without passage of plasma through the dextran sulfate column) did not modify serum lipids, hemodynamic parameters, or viscosity values. CONCLUSIONS: Low-density lipoprotein apheresis produces potentially useful hemodynamic effects. They are not adequately explained by changes in blood viscosity alone and might reflect a restoration of endothelium-mediated vasodilation, which is inhibited by high concentrations of low-density lipoprotein.
Adolescent↗