| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Development of unesterified cholesterol-rich lipid particles in atherosclerotic lesions of WHHL and cholesterol-fed NZW rabbits Chao, F. F., E. J. Blanchette-Mackie, et al. (1994), J Lipid Res 35(1): 71-83. Abstract: Previously, we isolated and characterized unesterified cholesterol-rich lipid particles (UCLP) that accumulate in extracellular spaces of atherosclerotic lesions of humans and cholesterol-fed rabbits. In the present study, we examined early developing atherosclerotic lesions to determine when UCLP appear and when they become enriched in cholesterol and sphingomyelin. Cholesterol-fed NZW rabbits, which rapidly develop atherosclerotic lesions, and genetically hyperlipidemic WHHL rabbits, which develop lesions over a longer period of time, were studied. UCLP of peak density 1.04 g/ml appear as early as 4 weeks after the onset of cholesterol feeding and progressively accumulate during atherosclerotic lesion development. Beginning with their appearance and afterwards, UCLP contain a saturating level (2:1 molar ratio) of cholesterol relative to phospholipid. Whereas, early UCLP are enriched in phosphatidylcholine, with time UCLP become enriched with sphingomyelin. Another UCLP population having a peak density of 1.09 g/ml was present in control aortas and increased in amount more slowly than the d 1.04 g/ml UCLP during cholesterol feeding. The d 1.09 g/ml particles were predominantly unilamellar vesicles, the majority between 100 and 200 nm in diameter. They contained > 90% of their cholesterol in unesterified form and their ratio of unesterified cholesterol to phospholipid progressively increased from 0.6 to 1.7 during cholesterol feeding. Liposome resistance to solubilization by high density lipoproteins is known to be increased by enrichment with unesterified cholesterol and sphingomyelin. Sphingomyelin enrichment of unesterified cholesterol-rich lipid particles (UCLP) could stabilize cholesterol in a form that does not readily crystallize. However, at the same time, the early and progressive accumulation of UCLP in developing atherosclerotic lesions may limit reverse cholesterol transport and accelerate disease progression. |
| Developmental expression of elements of hepatic cholesterol metabolism in the rat Smith, J. L., S. R. Lear, et al. (1995), J Lipid Res 36(4): 641-52. Abstract: The expression of several key enzymes and receptors of rat hepatic cholesterol metabolism was studied during development. Among major findings were: acyl coenzyme A:cholesterol acyltransferase, the cholesteryl ester hydrolases, cholesterol-7 alpha-hydroxylase and the alpha 2-macroglobulin receptor (LRP) were very low in fetal livers, but all were induced shortly before birth, suggesting that these elements are important for extrauterine life. Although the other elements continued to increase, by day 6 of postnatal life, cholesterol-7 alpha-hydroxylase had reached undetectable levels. It reappeared by day 12 of suckling, placing it in the group of late-appearing activities necessary for the fully mature hepatic phenotype. Changes in acyl coenzyme A:cholesterol acyltransferase activity appeared due predominantly to changes in amount of active protein. The cholesteryl ester hydrolase (CEH) activities all showed different developmental patterns, suggesting that each was a unique activity. The bile salt-dependent CEH activity was much higher in the suckling period than in the adult where it was almost undetectable, suggesting that this CEH may have its major importance in the suckling period of development. Low density lipoprotein receptors exhibited a pattern very different from that of the alpha 2-macroglobulin receptors and did not show consistent correlation with any other elements. At some developmental time points, the relationships amongst the elements differed significantly from the adult pattern. These studies provide for the first time an integrated picture of developmental expression of key elements of hepatic cholesterol metabolism and set the stage for further studies on their modes of regulation. |
| Developmental regulation of the expression of genes encoding proteins involved in cholesterol homeostasis Ness, G. C. (1994), Am J Med Genet 50(4): 355-7. Abstract: The developmental patterns of expression of HMG-CoA reductase, farnesyl pyrophosphate synthase, cholesterol 7 alpha-hydroxylase, and LDL receptor were investigated using Northern blotting analysis to quantitate mRNA levels. It was found that HMG-CoA reductase and farnesyl pyrophosphate synthase mRNA levels in brain reached peaks at age 4 days which correlates with the time of peak enzyme activity and the onset of rapid brain growth and myelination. In liver, HMG-CoA reductase and cholesterol 7 alpha-hydroxylase mRNA both rose dramatically at weaning. This is consistent with the concept that de novo synthesized cholesterol is the preferred substrate for cholesterol 7 alpha-hydroxylase and may also be involved in the induction of the enzyme. In testes, HMG-CoA reductase activity was highest at age 21 days and then declined, while LDL receptor mRNA levels rose from age 31 to 120 days. These studies suggest a major role for de novo cholesterol synthesis in developing brain, liver, and testes. |
| Developmental sensitivity of associative learning to cholesterol synthesis inhibitors O'Brien, W. T., G. Xu, et al. (2002), Behav Brain Res 129(1-2): 141-52. Abstract: Patients with Smith-Lemli-Opitz syndrome, a genetic disorder associated with severe mental retardation, are unable to convert 7-dehydrocholesterol to cholesterol. Treatment of rats with agents that block cholesterol synthesis produces a sterol profile reminiscent of Smith-Lemli-Opitz patients i.e., low levels of cholesterol accompanied by the appearance of its immediate precursor 7-dehydrocholesterol. In previous work, chronic inhibition of cholesterol synthesis in just-weaned rats impaired acquisition of the classically conditioned eyeblink response. The present study had two primary goals--(1) to determine whether the learning impairment depended on the age in which treatment was initiated; and (2) to determine whether the deficit was associative or due to performance factors. Consistent with earlier work, acquisition of the eyeblink conditioned response was impaired when the 30-day treatment was initiated on postnatal day (PND) 21. Reactivity to acoustic stimuli and to eyelid stimulation were normal, suggesting that the learning impairment was associative in nature. The learning impairment was transitory; acquisition was normal when evaluated 30 days after the cessation of treatment. When treatment was initiated 30 days after weaning (PND 51), acquisition of the eyeblink response was normal. However, brain sterols of young adult rats were less affected than those of just-weaned rats. Thus, there is a developmental sensitivity to cholesterol synthesis blocking agents both in terms of their effects on brain sterols and new motor learning. |
| Deviations from maximum weight predict high-density lipoprotein cholesterol levels in runners: the National Runners' Health Study Williams, P. T. (1997), Int J Obes Relat Metab Disord 21(1): 6-13. Abstract: OBJECTIVE: The inverse relationship between adiposity and high-density lipoprotein (HDL) cholesterol is well established, however, we believe that its usual representation lacks an important dimension. The purpose of this study is to test whether the relationship depends upon past weight history in addition to current weight. DESIGN: Physician-supplied medical data were compared to questionnaires from a national cross-sectional survey. SUBJECTS: 6847 men who ran between zero and 171 km per week. MEASUREMENTS: Self-reported current weight, greatest lifetime weight and body circumferences were compared to physician-supplied data for plasma concentrations of HDL cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. RESULTS: Current HDL-cholesterol levels were greatest in those runners with the greatest weight loss since their maximum lifetime weight and the greatest reductions in circumference of their waist, hip, and chest since their maximum weight. Plasma levels of triglycerides, LDL-cholesterol, and total cholesterol/HDL-cholesterol were also significantly lower for runners showing the greatest decreases in total and regional adiposity since their maximum weight. The results remained significant when adjusted for current body mass index and running mileage. CONCLUSION: These results suggest that the lipoprotein concentrations of runners are in part dependent upon whether the current weight is relatively high or low within the historical range of weights experienced by the individual. |
| Dexamethasone impairs cholesterol egress from a localized lipoprotein depot in vivo Stein, O., Y. Dabach, et al. (1998), Atherosclerosis 137(2): 303-10. Abstract: Plasma high density lipoproteins play a central role in the prevention and regression of atherosclerosis, as they are known to promote egress of cholesterol from cells. Glucocorticoids increase plasma HDL, but enhance esterification of cholesterol in macrophages in vitro. A novel model to measure cholesterol egress from a well defined depot in vivo was used currently to study the effect of dexamethasone on reverse cholesterol transport. Cationized LDL (cat LDL) (200 microg cholesterol) was injected into the rectus femoris muscle of mice and the egress of cholesterol was studied as a function of time. Daily subcutaneous injection of dexamethasone (1.25 microg) raised plasma HDL levels by 40-80%. In mice injected with cat LDL labeled with 3H-cholesterol, daily treatment with dexamethasone slowed the loss of labeled cholesterol from the depot. With dexamethasone, there was no removal of the mass of lipoprotein cholesterol up to 14 days after injection of cat LDL, while in the controls 75% of the exogenous cholesterol mass had been cleared from the depot. When the cat LDL had been labeled with 3H-cholesteryl ester (3H-CE), apparent hydrolysis of 3H-CE amounted to 46, 75 and 97% in controls, but only to 20, 48 and 65% in dexamethasone treated mice on days 4, 8 and 14, respectively. In addition, dexamethasone stimulated cholesterol re-esterification as evidenced by recovery of 80% of the retained cholesterol mass as CE. In experiments with cultured macrophages exposed to modified LDL, dexamethasone increased the amount of labeled cholesteryl ester by 50-75% as compared to controls. Histological examination of the rectus femoris muscle after injection of cat LDL showed that in dexamethasone treated mice cellular infiltration was sparser on day 4, but not on day 8, and persisted longer than in controls. In conclusion, dexamethasone treatment impeded cholesterol egress from a lipoprotein depot by: a) reduction of early inflow of mononuclear cells; b) partial inhibition of cholesteryl ester hydrolysis, and c) enhancement of cholesterol esterification. The latter effect did not permit cholesterol egress from the injected site even in the presence of high plasma HDL in dexamethasone treated mice. |
| Dexamethasone inhibits macrophage accumulation after balloon arterial injury in cholesterol fed rabbits Poon, M., S. D. Gertz, et al. (2001), Atherosclerosis 155(2): 371-80. Abstract: Macrophages play a critical role in the development and progression of atherosclerosis. This study was designed to examine the effect of the glucocorticoid, dexamethasone, (Dex), on macrophage accumulation after acute arterial injury. Twenty New Zealand white rabbits were fed a 2% cholesterol, 6% peanut oil, rabbit chow diet for one month prior to bilateral balloon dilatation of the femoral arteries. Ten rabbits received Dex (1 mg/kg, im.) the day before and then daily for 7 days after arterial injury; control rabbits received vehicle only. Seven days after injury, Dex treatment resulted in a 96% and 77% reduction (P < 0.002) in the mean number of macrophages accumulating in the intima and media, respectively. This effect was apparently not due to a reduction in the number of circulating monocytes or to the ability of monocytes from Dex treated animals to adhere to endothelium or migrate in response to a chemotactic signal, determined in vitro under static conditions. It was associated with a 61% reduction in monocyte chemoattractant protein-1 (MCP-1) antigen (P < 0.004) in the injured arterial wall (media+intima). Glucocorticoids may be useful in attenuating the inflammatory response and subsequent foam-cell accumulation after arterial injury. |
| Dexamethasone-dependent modulation of cholesterol levels in human lymphoblastoid B cell line through sphingosine production Miccheli, A., A. Tomassini, et al. (1994), Biochim Biophys Acta 1221(2): 171-7. Abstract: The effect of dexamethasone on lipid composition of Epstein-Barr virus transformed human B lymphocytes have been investigated by 31P- and 1H-NMR spectroscopy and compared to the effects due to exogenous sphingosine treatment. Furthermore, the effects of dexamethasone and sphingosine on membrane structure was evaluated by fluorimetry. No significant changes were evidenced in phospholipid composition and in the ratio of unsaturated to total fatty-acid chains. A significant increase in total cholesterol levels was evident at 30 min incubation with dexamethasone or sphingosine; a parallel increase in DPH polarization at 30 min was also demonstrated. TMA-DPH intensity measurements suggest a slowing of vesicular intracellular traffic due to the treatment. The results suggest a dexamethasone- and sphingosine-dependent inhibition of intracellular cholesterol transport. |
| Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol-fed rabbits. Possible mechanisms Asai, K., C. Funaki, et al. (1993), Arterioscler Thromb 13(6): 892-9. Abstract: We investigated the mechanisms by which corticosteroids affect atherosclerosis. Male New Zealand White rabbits were injected with 0.125 mg dexamethasone (n = 10) or vehicle (control group, n = 10). Both groups were fed a 1% cholesterol diet for 8 weeks. Although the dexamethasone-treated animals exhibited a greater degree of hyperlipidemia, they exhibited significantly less atherosclerotic plaque of the aortic surface than control animals (7.8% versus 47.2%). Immunofluorescence study of the aortic plaque specimens showed that dexamethasone administration reduced both macrophages and T lymphocytes. In vitro, dexamethasone suppressed the proliferation and differentiation of U937 cells and inhibited uptake and degradation of beta-very low density lipoproteins by mouse peritoneal macrophages. These findings suggest that dexamethasone suppresses the development of atherosclerosis in the aorta of rabbits by inhibiting recruitment and proliferation of macrophages and the formation of foam cells in plaques. |
| Dextran sulfate complexes with potassium phosphate to interfere in determinations of high-density lipoprotein cholesterol Olmos, J. M., M. A. Lasuncion, et al. (1992), Clin Chem 38(2): 233-7. Abstract: The interference of dextran sulfate with the colorimetric determination of free cholesterol causes an increase in the absorbance that is proportional to the dextran sulfate concentration in the sample. This makes estimation of the free cholesterol concentration unreliable in high-density lipoprotein-containing supernates obtained after plasma precipitation with dextran sulfate/MgCl2. Analysis of the absorption spectrum demonstrated that the absorbance increase was due to turbidity. We observed this effect with colorimetric reagents based on potassium phosphate buffer but not with those based on sodium phosphate or Tris buffers. This effect is ascribed to dextran sulfate because neither the omission of Mg2+ ions nor their chelation with EDTA prevented turbidity, whereas precipitation of dextran sulfate with Ba2+ counteracted this effect. Therefore, potassium phosphate-buffered reagents appear unsuitable for colorimetric lipid determinations in samples containing dextran sulfate. |
| Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism Thompson, C. J., S. M. Ross, et al. (2004), Endocrinology 145(3): 1227-37. Abstract: In utero exposure to di(n-butyl) phthalate (DBP) leads to a variety of male reproductive abnormalities similar to those caused by androgen receptor antagonists. DBP demonstrates no affinity for the androgen receptor, but rather leads to diminished testosterone production by the fetal testis. The purpose of this study was to determine the onset and reversibility of DBP effects on the fetal testis and to determine at a functional level the points in the cholesterol transport and steroidogenesis pathways affected by DBP. Starting at gestational day (gd) 12, pregnant rats were gavaged daily with 500 mg/kg DBP or corn oil control. Significant decreases in testosterone production and mRNA expression of scavenger receptor B1, P450(SCC), steroidogenic acute regulatory protein, and cytochrome p450c17 were observed as early as gd 17. Testosterone, mRNA, and protein levels remained low 24 h after withdrawal of DBP treatment but increased 48 h after cessation of DBP exposure. In another experiment, pregnant dams were treated with DBP until gd 19, with the start of DBP treatment moved 1 d later into gestation for each treatment group, with the final group dosed only on gd 19. Significant decreases in testosterone, mRNA expression, and protein expression were evident as early as 3 h after treatment with DBP, with full repression apparent 24 h after treatment. Using a testis explant system, we determined that DBP treatment led to diminished transport of cholesterol across the mitochondrial membrane as well as diminished function at each point in the testosterone biosynthesis pathway except 17 beta-hydroxysteroid dehydrogenase. The transcriptional repression caused by DBP does not appear to be mediated via interference with steroidogenic factor-1 as determined by reporter assays. We conclude that high-dose DBP exposure leads to rapid and reversible diminution of the expression of several proteins required for cholesterol transport and steroidogenesis in the fetal testis, resulting in decreased testosterone synthesis and consequent male reproductive maldevelopment. |
| Diabetes and cholesterol metabolism: the succinate hypothesis Ertel, N. H. (2003), Diabetes Care 26(2): 549-50; discussion 550. |
| Diabetes contributes to cholesterol metabolism regardless of obesity Simonen, P. P., H. K. Gylling, et al. (2002), Diabetes Care 25(9): 1511-5. Abstract: OBJECTIVE: To investigate cholesterol metabolism in obesity with and without diabetes. RESEARCH DESIGN AND METHODS: We performed cross-sectional metabolic studies in obese individuals with and without type 2 diabetes. The study population consisted of 16 obese (BMI >30 kg/m(2)) diabetic subjects with a mean age of 52 +/- 2 years (SE) and 16 nondiabetic control subjects of similar age and weight. Cholesterol absorption efficiency was measured with peroral dual isotopes and cholesterol synthesis with sterol balance. RESULTS: Serum total cholesterol did not differ between the groups, but LDL and HDL cholesterol were significantly lower and VLDL cholesterol and serum total and VLDL triglycerides were higher in the diabetic group than in the control group. Cholesterol absorption efficiency was 29 +/- 1% in diabetic subjects vs. 42 +/- 2% in the control subjects (P < 0.01). Cholesterol synthesis was higher (17 +/- 1 vs. 14 +/- 1 mg. kg(-1). day(-1); P < 0.05) and neutral sterol and bile acid excretion and cholesterol turnover tended to be higher in the diabetic group than in the control group. Blood glucose was positively related to cholesterol synthesis in the diabetic group (r = +0.663, P < 0.01) and in the control group (r = +0.590, P < 0.05), suggesting that the higher blood glucose level, the higher the cholesterol synthesis. In addition, blood glucose was significantly positively related to fecal neutral sterol excretion in both groups. CONCLUSIONS: Cholesterol absorption efficiency was lower and cholesterol synthesis was higher in obese subjects with diabetes than in those without diabetes, suggesting that diabetes modulates cholesterol metabolism more than obesity alone. |
| Diabetes, hemoglobin A(1c), cholesterol, and the risk of moderate chronic renal insufficiency in an ambulatory population Hsu, C. Y., D. W. Bates, et al. (2000), Am J Kidney Dis 36(2): 272-81. Abstract: Moderate chronic renal insufficiency is common, with 12.5 million individuals in the United States estimated to have a creatinine clearance less than 50 mL/min/1.73 m(2). Little is known about the risk factors for moderate chronic renal insufficiency. We studied 1, 428 subjects with Cockcroft-Gault-estimated creatinine clearances greater than 70 mL/min in a hospital-based ambulatory population. Over a mean of 5.7 +/- 1.3 years, 86 subjects developed moderate chronic renal insufficiency, defined as a decrease in creatinine clearance to less than 60 mL/min (1.1 case/100 person-years). Risk factors for moderate chronic renal insufficiency were identified using a proportional hazards model controlling for age, sex, race, systolic blood pressure, and angiotensin-converting enzyme (ACE) inhibitor use. The risk for developing moderate chronic renal insufficiency was associated with diabetes mellitus (relative risk, 2.1; 95% confidence interval CI, 1.3 to 3.3) and elevated hemoglobin A(1c) levels. Compared with subjects with normoglycemia (hemoglobin A(1c) 9.0%) was 2.7 (95% CI, 1.4 to 5.1). The development of moderate chronic renal insufficiency was also independently predicted by elevated maximum serum cholesterol level. Compared with subjects with maximum cholesterol levels of 250 mg/dL or less, the relative risk for those with maximum cholesterol levels greater than 350 mg/dL was 2.4 (95% CI, 1.1 to 5.2). Similar relative risks were obtained when moderate chronic renal insufficiency was defined by the development of an increase in serum creatinine level. Hypercholesterolemia was also associated with moderate chronic renal insufficiency among persons without diabetes. In conclusion, the risk for developing moderate chronic renal insufficiency is increased by diabetes and elevated hemoglobin A(1c) and serum cholesterol levels. Modification of these risk factors may decrease the incidence of moderate chronic renal insufficiency. |
| Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low HDL cholesterol levels Ginsberg, H. N. (1996), Diabetes 45 Suppl 3: S27-30. Abstract: Elevated levels of plasma triglycerides (TG) and reduced concentrations of HDL cholesterol are very common in patients with diabetes, particularly NIDDM. Although regulation of the plasma concentrations of VLDL, the major TG-rich lipoprotein is extremely complex, it is clear from in vivo kinetic studies that increased rates of secretion of VLDL into plasma is almost uniformly present in patients with NIDDM and hypertriglyceridemia. Recent studies at the cellular level indicate that increased fatty acid flux to the liver, also common in NIDDM (and other insulin-resistant states associated with elevated plasma TG levels), will stimulate the assembly and secretion of apoprotein (apo) B-containing lipoproteins by targeting apoB for secretion rather than intracellular degradation. Increased rates of secretion of VLDL into plasma appears to drive the exchange of TG from these lipoproteins for HDL cholesteryl ester. This exchange, which occurs in plasma, is facilitated by cholesteryl ester transfer protein, and generates a TG-enriched HDL that is a substrate for either hepatic lipase or lipoprotein lipase. When the TG in HDL is hydrolyzed, the resultant particle is smaller, and this appears to affect the binding of the major HDL protein, apoA-I. ApoA-I dissociates from the smaller, lipid-poor HDL, and the free apoA-I (molecular weight 28,000) can be filtered by the glomerulus in the kidney and most likely is degraded in renal tubular cells after reabsorption. Thus, increased free fatty acid transport in plasma, a common abnormality in insulin-resistant states, may be the underlying driving force for the two common lipid abnormalities seen in diabetes. |
| Diabetic postprandial triglyceride-rich lipoproteins increase esterified cholesterol accumulation in THP-1 macrophages Georgopoulos, A., S. D. Kafonek, et al. (1994), Metabolism 43(9): 1063-72. Abstract: The risk of cardiovascular disease is increased in subjects with insulin-dependent diabetes mellitus (IDDM), although the mechanism remains unclear. To assess whether diabetic postprandial triglyceride (TG)-rich lipoprotein (TGRLP) subfractions (Sf > 400, 100-400, and 20-100) isolated from non-obese, normolipidemic IDDM subjects (n = 14) are potentially more atherogenic than lipoproteins from normal controls (n = 13), we measured cholesteryl ester (CE) synthesis and esterified cholesterol (EC) mass accumulation in THP-1 macrophages incubated with postprandial TGRLP. Diabetic Sf > 400 and Sf 100-400 but not Sf 20-100 significantly increased the mean (+/- SE) rate (pmol/mg cell protein/24 h) of CE synthesis in THP-1 macrophages compared with normal controls (Sf > 400, 673 +/- 26 v 301 +/- 64, P <.025; Sf 100-400, 560 +/- 27 v 298 +/- 39, P <.0005; Sf 20-100, 743 +/- 51 v 831 +/- 45). As well, all three diabetic TGRLP increased the mass of EC (microgram EC/mg cell protein/48 h) as compared with normal controls (Sf > 400, 4.9 +/- 0.61 v 2.9 +/- 0.50, P <.025; Sf 100-400, 5.7 +/- 0.91 v 3.4 +/- 0.34, P <.05; Sf 20-100, 5.4 +/- 0.7 v 3.2 +/- 0.52, P <.05). This effect is sustained for at least 7 hours postprandially and is greater than that of fasting Sf 100-400 (P <.03) and Sf 20-100 (P <.05) and similar to malondealdehyde low-density lipoprotein (MDA-LDL). To assess the mechanisms involved, the chemical composition and cellular degradation of diabetic and control lipoproteins were compared. Postprandial diabetic Sf 100-400 had abnormal composition (phospholipid to protein ratio, 1.86 +/- 0.14 v 1.5 +/- 0.13, P <.05) and in preliminary experiments demonstrated increased cell association (mean +/- SD at 6 hours, 126 +/- 34.3 v 57 +/- 4.2) and degradation (584 +/- 141 v 254 +/- 13) compared with that of normal controls, and may account for the observed increase in EC accumulation. In summary, postprandial diabetic Sf > 400 and Sf 100-400 TGRLP increase CE synthesis and Sf > 400, Sf 100-400, and Sf 20-100 lipoproteins increase EC accumulation in human macrophages compared with normal control lipoproteins. Diabetic Sf 100-400 lipoproteins have abnormal composition and seem to have increased cellular association and degradation compared with normal lipoproteins. Our findings suggest a role for postprandial TGRLP in the increased risk of cardiovascular disease among subjects with IDDM. |
| Diagnosing ascites: value of ascitic fluid total protein, albumin, cholesterol, their ratios, serum-ascites albumin and cholesterol gradient Gupta, R., S. P. Misra, et al. (1995), J Gastroenterol Hepatol 10(3): 295-9. Abstract: Ascitic fluid total protein, albumin, cholesterol, their ascites/serum ratios, serum-ascites albumin and cholesterol gradients were measured for their ability to differentiate cirrhotic, malignant and tuberculous ascites in 76 patients. The mean +/- s.d. ascitic fluid total protein, albumin, cholesterol, their respective ascitic fluid/serum ratios in cirrhotic ascites were lower than malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was significant for ascitic fluid/serum total protein (P < 0.05) and ascitic fluid/serum albumin (P < 0.01) only. Mean serum-ascites albumin gradient in cirrhotics was higher than in the malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was significant (P < 0.01). Mean +/- s.d. serum-ascites cholesterol gradient in cirrhotics was higher than that in malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was also significant (P < 0.01). Both serum/ascitic fluid total protein less than 0.5 and ascitic fluid cholesterol less than 55 mg/dL had 94% diagnostic accuracy for differentiating cirrhotic from malignant and tuberculous differentiating cirrhotic from malignant and tuberculous ascites. Serum ascitic fluid albumin gradient greater than 1.1 g/dL, ascitic fluid/serum albumin less than 0.65 and ascitic fluid albumin less than 2 g/dL had diagnostic accuracy of 92, 92 and 91%, respectively. Ascitic fluid total protein had diagnostic accuracy of 88%. None of the tests was able to differentiate between malignant and tuberculous ascites. Measurement of ascitic fluid cholesterol concentration is a simple method of differentiating cirrhotic from non-cirrhotic ascites. |
| Diagnosis of neoplastic ascites: combined use of albumin gradient between serum and ascites and cholesterol in ascitic fluid Sartori, M., S. Andorno, et al. (1996), Recenti Prog Med 87(2): 75-7. |
| Diagnostic accuracy of radionuclide imaging using 131I nor-cholesterol or meta-iodobenzylguanidine in patients with hypersecreting or non-hypersecreting adrenal tumours Maurea, S., M. Klain, et al. (2002), Nucl Med Commun 23(10): 951-60. Abstract: The aim of this retrospective study was to evaluate the diagnostic accuracy of nor-cholesterol and meta-iodobenzylguanidine radionuclide imaging in two separate groups of patients with adrenal tumours to characterize lesions as adenoma or pheochromocytoma. We studied 75 patients (22 male and 53 female, mean age 47 +/- 15 years) with hypersecreting (n = 32) or non-hypersecreting (n = 43) unilateral adrenal tumours detected by computerized tomography or magnetic resonance scans. 131I nor-cholesterol adrenal scintigraphy was performed in 41 patients. Meta-131Iiodobenzylguanidine (131I-MIBG) imaging was acquired in the other 34 patients. Pathology examinations (n = 58) or computerized tomography follow-up studies (n = 17) were obtained. Adrenal lesions were represented by 44 adenomas, four cysts, one myelolipoma, one pseudotumour, one ganglioneuroma, 16 pheochromocytomas, three carcinomas, four metastases and one sarcoma. Radionuclide studies were qualitatively evaluated and the corresponding results were classified as true positive, true negative, false positive and false negative. Diagnostic sensitivity, specificity and accuracy as well as positive and negative predictive values were calculated. The diagnostic values of nor-cholesterol scintigraphy in identifying adrenal adenomas were sensitivity 100%, specificity 71%, accuracy 95%, positive predictive value 94% and negative predictive value 100%; of note, two false positive cases were observed represented by a pheochromocytoma and a myelolipoma. The diagnostic values of MIBG scintigraphy in recognizing pheochromocytoma were sensitivity 100%, specificity 95%, accuracy 97%, positive predictive value 94% and negative predictive value 100%; only one false positive case occurred consisting of a carcinoma. It is concluded that, in the large majority of cases, adrenal scintigraphy using nor-cholesterol or MIBG is able to characterize specific lesions such as adenoma and pheochromocytoma, respectively. These findings show relevant clinical impact, particularly in patients with non-hypersecreting adrenal lasions. Radiotracer selection depends on clinical patient history and department availability; since benign adenomas are the most common cause of non-hypersecreting tumours, nor-cholesterol should be the first choice followed by MIBG if nor-cholesterol shows normal images. However, rare as well as unusual findings may be observed; nor-cholesterol uptake may occasionally be also found in non-adenoma tumours such as myelolipoma and pheochromocytoma. Similarly, MIBG accumulation may occur not only in lesions arising from medullary chromaffin tissue, but also rarely in cortical adrenal carcinoma. |
| Diagnostic image (57). Tenosynovial swelling with cholesterol crystals in rheumatoid arthritis Jacobs, J. W. and J. W. Bijlsma (2001), Ned Tijdschr Geneeskd 145(39): 1886. Abstract: In a 69-year-old female patient with erosive rheumatoid arthritis for 8 years, aspiration of a tenosynovial swelling on the dorsum of the right wrist yielded a puslike substance with many birefringent platelike cholesterol crystals. |