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PubMed2006

High glucose increases the expression of Cbfa1 and BMP-2 and enhances the calcification of vascular smooth muscle cells.

BACKGROUND: Vascular calcification is common in diabetes but the pathogenesis is poorly understood. METHODS: To investigate the pathogenesis, we first examined the histology of inferior epigastric arteries from diabetic and non-diabetic patients undergoing a renal transplant. To examine the role of hyperglycaemia, bovine vascular smooth muscle cells (BVSMCs) were incubated with normal (5 mM) or high glucose (25 mM) for 48 or 72 h. RESULTS: The results demonstrated that diabetic patients, compared with non-diabetic patients, had significantly greater calcification and increased expression of the bone matrix proteins osteopontin, type I collagen, bone sialoprotein and alkaline phosphatase (ALP). The in vitro studies demonstrated that high glucose increased the expression of the osteoblast transcription factor core binding factor alpha subunit 1 (Cbfa1) and its downstream protein osteocalcin by 1.9-fold and 1.8-fold, respectively, and ALP activity by 1.5-fold. These findings were blunted in the presence of an inhibitor to protein kinase C. High glucose also significantly enhanced calcification in BVSMC in a time-dependent manner (2.20 +/- 0.50 vs 1.35 +/- 0.55 micromol/mg, day 7; 5.04 +/- 1.35 vs 3.12 +/- 0.92 micromol/mg, day 14; P < 0.05). High glucose also induced the secretion of bone morphogenetic protein-2, a known osteoinductive factor, and further increased the secretion normally seen during calcification by 43% at day 7 and 57% at day 14. CONCLUSIONS: These results demonstrate that vascular calcification in patients with diabetes is a cell-mediated process characterized by a phenotypic change of VSMCs to osteoblast-like cells with increased bone matrix protein expression, and that hyperglycaemia may directly induce these changes.

Animals↗
PubMed2006

Factors involved in vascular calcification and atherosclerosis in maintenance haemodialysis patients.

BACKGROUND: Atherosclerosis and vascular calcifications are common causes of morbidity and mortality in maintenance haemodialysis patients. In addition to the well-known traditional risk factors, uraemia-specific factors appear to enhance dramatically the progression of the pathological processes involved. The aim of the present study was to evaluate the degree of atherosclerosis and vascular calcifications in chronic haemodialysis patients using non-invasive imaging methods, and to identify potentially involved factors. METHODS: The study included 73 patients (36 females, 37 males), aged 25-75 years, who were on haemodialysis treatment for 12-275 months (mean dialysis vintage 73.8 months). We assessed the following circulating parameters: calcium (Ca), phosphorus, 'intact' parathyroid hormone (iPTH), 25OH vitamin D, lipids, oxidized LDL (ox-LDL), Lp(a), homocysteine, leptin, IL-1-beta, IL-6, CRP, TGF-beta, TNF-alpha, (PDGF), advanced oxidation protein products (AOPP) and myeloperoxidase activity (MPO). Coronary artery calcification score (CACS) was assessed using multi-row spiral CT (MSCT). Intima-media thickness index of the common carotid artery (CCA-IMT) and presence of cervical artery atherosclerotic plaques were evaluated by ultrasonography. RESULTS: Coronary artery calcifications were observed in 79.5% of the patients, with CACS ranging from 0 to 4987. In univariate analysis, a positive correlation was observed between CACS and age, BMI, iPTH, CRP, IL-6 and CCA-IMT, whereas an inverse correlation existed with 25OH vitamin D, TGF-beta and PDGF. CCA-IMT ranged from 0.4 to 1.1 mm. It was positively correlated, in univariate analysis, with age, CACS, CRP and Il-6, and negatively with 25OH vitamin D, TGF-beta and PDGF. Only CACS remained as independent predictive factor of CCA-IMT in multivariate analysis. Atherosclerotic plaques were found in the carotid arteries of 53 patients (72%). The number of plaques was positively correlated with age, CACS, phosphorus, MPO, CRP and IL-6, and inversely with 25OH vitamin D in univariate analysis. In multivariate regression analysis, only age and CACS remained as independent variables. CONCLUSION: In addition to classic risk factors, the degree of atherosclerosis and vascular calcification in our dialysis patient population were associated with several factors that are frequently abnormal in advanced chronic renal failure, but except age, all of them were interdependent. Notably, as in the general population, CACS was an independent predictor of the degree of atherosclerosis in haemodialysis patients.

Adult↗
PubMed2006

Development of a cardiovascular calcification index using simple imaging tools in haemodialysis patients.

BACKGROUND: Coronary artery calcification (CAC) is highly prevalent in haemodialysis patients and is associated with cardiovascular outcomes. Though cardiac computed tomography (CCT) is accurate, it is not widely available. METHODS: We developed a cardiovascular calcification index (CCI) to predict the presence of CAC for haemodialysis patients using simple in-office techniques. Prevalent haemodialysis patients (n = 140) underwent CCT imaging for CAC, a lateral abdominal X-ray for calcification of the abdominal aorta, an echocardiogram for valvular calcification, and pulse pressure measurement. A CCI was derived by weighting the prevalence rate ratios of CAC > or =1000. Using bootstrap techniques, validation was performed using receiver operator characteristic curves and likelihood ratios. RESULTS: Points were assigned for patients' age (60-69 and > or =70 years, 1 and 2 points, respectively), dialysis vintage > or =2 years (1 point), aortic and mitral valve calcification (3 and 1 points, respectively), and abdominal aorta X-ray scores of 1-6 and > or =7 (2 and 4 points, respectively). Race, sex and pulse pressure did not contribute to the CCI. The CCI ranged from 0 to 11 points. The likelihood ratio of CAC > or =1000 associated with CCI scores of 2-4, 5, 6-8 and 9-11 were 1.28, 2.03, 2.94 and 3.83, respectively. Given the prevalence of CAC > or =1000 of 21% in the current study, the probability of having CAC > or =1000 was 26%, 38%, 43% and 50% for participants with CCI scores of 2-4, 5, 6-8, and > or =9, respectively. CONCLUSIONS: Although refinement is needed, the CCI developed in the current study provides an alternative for predicting CAC when CCT is not available.

Adult↗
PubMed1993

Tendon calcifications of the hip adductors in chondrocalcinosis: a radiological study of 75 patients.

Studies on tendon involvement in articular chondrocalcinosis (ACC) are scarce, with little data focusing on its prevalence and characteristics. We carried out a radiological survey on 75 patients with ACC in order to establish the frequency and radiological appearance of calcific deposits at the origin of the adductor tendons on the ischium. In 19 of these patients, radiological visible linear calcifications compatible with chondrocalcinosis were observed at this site. There is a high correlation between the existence of pelvic tendon calcifications and the extension and intensity of calcific deposits in other articular areas. Calcifications of the adductor tendons are not uncommon in ACC, the amount of calcium pyrophosphate deposits may be the most important factor leading to tendon involvement in this disorder.

Adult↗
PubMed1999

Elemental analysis and clinical implications of calcification deposits associated with silicone breast implants.

Calcification of the fibrous capsule surrounding silicone breast implants is a well-recognized occurrence that increases with time following implantation. These mineralized deposits potentially confound mammographic breast cancer surveillance already made difficult by the obscuring effects of silicone breast implants. The authors performed elemental analysis of silicone breast implant-associated calcifications to define better their chemical composition as related to mammographic and clinical significance. Electron probe microanalysis and infrared spectroscopy revealed all of the calcification deposits to be calcium complexed with tribasic phosphate. No evidence of calcium oxalate, calcium carbonate, silicone, or talc was observed. Caution must be employed in interpreting mammograms in women with silicone breast implants as well as those who have had their silicone breast implants removed. High-density mammographic calcifications indicative of calcium phosphate associated with a silicone breast implant may represent an accepted consequence of implantation or nearby carcinoma. We recommend baseline mammography on women who have had their silicone breast implants removed to prevent unnecessary fine-needle aspiration or tissue biopsy of retained breast capsule calcifications during subsequent routine surveillance for carcinoma.

Breast↗
PubMed2003

Radiographic tools for assessment of pathologic cartilage calcification.

Both hyaline cartilage and fibrocartilage can calcify in a variety of pathologic conditions. Traditionally, plain film radiographs have been used to diagnose such calcifications; however, only when the calcifications have adequately mineralized are they radiographically apparent. Cross-sectional imaging modalities such as computed tomography, magnetic resonance imaging, and ultrasonography can often demonstrate cartilage calcifications before they are radiographically apparent, thus yielding earlier detection of disease processes. Cartilage calcifications have a distinct appearance on each of these various imaging modalities. A working knowledge of the typical locations of cartilage calcific deposits as well as their appearance on various imaging modalities is necessary for accurate diagnosis.

Arthrography↗
PubMedDate not supplied

Al+++ binding studies and metallic cation effects on bioprosthetic heart valve calcification in the rat subdermal model.

Al+++ preincubation has been shown to inhibit calcification of glutaraldehyde pretreated bovine pericardium calcification in the rat subdermal model. This study was designed to assess in vitro the Al+++ (10(-1) M, 10(-2) M, 10(-3) M preincubations) binding characteristics of glutaraldehyde pretreated bovine pericardium. In vivo studies assessed the ability of AlCl3 (10(-1) M, 10(-2) M, 10(-3) M) preincubations to inhibit calcification after 21 and 60 days in the rat subdermal model. Other in vivo studies investigated the ability of other metallic cations (Fe+++, La+++, and Ga+++) used as a pretreatment to inhibit glutaraldehyde pretreated bovine pericardium calcification after a 21 day rat subdermal implant. Lyophylized glutaraldehyde pretreated bovine pericardium samples were analyzed for Al+++ by neutron activation. In vitro results showed the greatest glutaraldehyde pretreated bovine pericardium Al+++ uptake in specimens incubated in 0.1M AlCl3. Maximal Al+++ uptake occurred by 1 hour. Glutaraldehyde pretreated bovine pericardium Al+++ levels after incubation in 10(-1) M, 10(-2) M, and 10(-3) M AlCl3 for 1 hour were 351.4 +/- 15.8 nM/mg, 96.4 +/- 17.4 nM/mg, and 24.6 +/- 4.9 nM/mg, respectively versus 394.5 +/- 48.0 nM/mg, 105.3 +/- 2.3 nM/mg, 40.0 +/- 8.8 nM/mg, respectively for 3 days. In vivo 21 day rat (50-60 g, male, Sprague-Dawley) subdermal implants of 0.1 M AlCl3, FeCl3, FeCl3 plus citrate, LaCl3, and GaNO3 pretreated glutaraldehyde pretreated bovine pericardium showed calcification inhibition by Al+++, Fe+++, and Fe+++ plus citrate (Ca++ = 5.5 +/- 0.2 micrograms/mg, 13.6 +/- 4.6 micrograms/mg, 5.9 +/- 1.7 micrograms/mg, respectively) compared to control (Ca++ = 63.6 +/- 5.7 micrograms/mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMedDate not supplied

Chemical modification of implantable biologic tissue for anti-calcification.

Biologic porcine tissue was modified by coupling sulfonated polyethyl-eneoxide (PEO-SO3) and the effect of modification on calcification was evaluated in vitro and in vivo. The modification process involves grafting PEO-SO3 to porcine valve leaflet either by carbodiimide (EDC) activation or by direct coupling using glutaraldehyde. Thermal property, measured by differential scanning calorimetry, showed that the shrinkage temperature of modified tissue increased compared with control tissue and fresh tissue, suggesting increased thermal stability. Resistance to collagenase digestion revealed that modified tissues have greater resistance to enzyme digestion than do control tissues. In vitro calcification showed that modified tissues have less calcium deposition than do control tissues. In vivo calcification, using a rat subcutaneous implantation model, also showed less calcification of modified tissue than that of control. The resistance of modified tissue to collagenase, higher shrinkage temperature, and reduced calcification, when compared with control tissue, attest to the usefulness of this chemical modification for implantable biologic tissue.

Animals↗
PubMed2001

Roentgenographic evaluation of ossification and calcification of the lumbar spinal canal after intradiscal betamethasone injection.

There have been reports of lumbar spinal canal ossification and calcification after triamcinolone intradiscal injection therapy. Our objective was to observe the roentgenographic changes after betamethasone intradiscal injection therapy for lumbar disc diseases. The subjects were 183 patients (498 discs; 130 men and 53 women) who underwent discography and betamethasone intradiscal injection therapy and were followed for a mean of 5 years and 7 months. Ossification and calcification appeared de novo (three patients, three discs) or enlarged (four patients, five discs) in the outer layer of the posterior annulus fibrosus or posterior longitudinal ligament in eight discs among seven patients (3.8%). The incidence and degree of ossification and calcification in our patients were significantly lower than those reported in previous studies, and a long time elapsed before ossification and calcification appeared or enlarged. Intradiscal injection of betamethasone did not appear to confer any incremental relative risk for lumbar spinal canal ossification and calcification based on review of follow-up roentgenographs.

Adolescent↗
PubMed1978

Detection of heterotopic calcification with 99mTc-pyrophosphate in spinal cord injury patients.

Whole body 99mTc-pyrophosphate scans were obtained and correlated with skeletal radiographs for detection of heterotopic calcification in 122 spinal injury patients. There were 27 patients with recent injury (less than 6 months) and 95 with injury of 6 months to 25 years duration. Ectopic calcification was detected in 8 of the 27 patients (30%) with recent injury and in 32 of the 95 (34%) with injury of over 6 months duration. Ectopic calcification seen on radiographs were also seen on scans in all instances. The scan was a sensitive indicator of the ectopic calcification particularly at its early stage, and detected its presence before observable radiographic changes in 5 patients with injury of 1-3 months duration. In 3 of the 5 patients, the ectopic calcification mimicked deep vein thrombosis in presentation, and the scan was valuable in identifying the nature of the complication.

Adult↗
PubMed1992

Multiple metastatic calcifications detected by bone scintigraphy and demonstrated by CT.

Metastatic calcifications according to histopathologic and scintigraphic findings have been well-defined. The authors report a postoperative case of hyperparathyroidism with multiple metastatic calcifications in the lung, kidney, stomach, heart, and vessels that were primarily detected by bone scintigraphy and demonstrated by CT. Tc-99m MDP bone scintigraphy showed a markedly increased accumulation of radioactivity diffusely throughout the lung, left ventricular wall, both kidneys, and the gastric cardia and body. In the lung, plain films showed almost normal lung. CT, however, demonstrated patchy, slightly increased densities in the lung bilaterally. Cardiac CT indicated a considerably increased density of the ventricular myocardium and remarkable calcification in or near the atrioventricular septum or annulus fibrosus. Upper abdominal CT demonstrated increased densities diffusely throughout the gastric mucosa and renal cortex. Only vascular calcifications were depicted by plain films. Using both bone scintigraphy and CT provides accurate information about each lesion and each tissue, allowing precise diagnosis of even a questionable lesion in the early stage of metastatic calcification. Early diagnosis and early therapy offer the best chance for cure or palliative therapy.

Bone and Bones↗
PubMed1995

Metastatic soft tissue calcification in chronic renal failure detected by radionuclide imaging.

Metastatic calcification has been reported in several disease entities, including chronic renal failure. Various imaging modalities have been shown to be useful in the detection of metastatic soft tissue calcification. Radionuclide imaging may detect metastatic soft tissue calcification more readily than routine diagnostic modalities and be a valuable noninvasive method to establish an early diagnosis in high-risk patients. The authors report a patient with extensive soft tissue metastatic calcification who had a myriad of clinical symptoms. The extensive calcification was detected with a radionuclide imaging.

Calcinosis↗
PubMedDate not supplied

X-ray appearance and clinical significance of left atrial wall calcification.

Ten patients with calcifications of the left atrium are reported with review of the literature. Calcification of the left atrium is frequently associated with history of rheumatic fever, longstanding congestive heart failure, atrial fibrillation, mural thrombus and embolization. Early recognition of such lesions is essential for the management of the patients, particularly when surgical intervention is contemplated. A practical classification of left atrial calcification is proposed according to the dominant lesion in each group: (a) Calcification of the left atrial appendage alone (Mitral stenosis). (b) cacification of all 3 component lesions of the left atrium, i.e., the left atrial appendage, the free wall, and the mitral valve (Severe mitral stenosis). (c) Calcification of the left atrium in MacCallum's patch alone (Mitral insufficiency).

Adult↗
PubMed1995

Calcification can shorten T2, but not T1, at magnetic resonance imaging fields. Results of a relaxometry study of calcified human meningiomas.

RATIONALE AND OBJECTIVES: Water content and water-proton relaxation rates are reported for fresh, histologically characterized, surgical specimens of calcified human intracranial meningiomas and compared with results for noncalcified meningiomas from an earlier study and with calcium hydroxyapatite (CaHA) suspensions to elucidate the influence of calcification on magnetic resonance imaging (MRI) signal intensity of calcified meningiomas. METHODS: The magnetic field dependence of 1/T1 of water protons (nuclear magnetic relaxation dispersion profile) and dry weights are reported for 38 calcified nonhemorrhagic and 3 hemorrhagic specimens of known histologic subtype, a subset of the 67 specimens measured earlier. Calcification was considered mild or heavy when the dry weight was within or above the range for noncalcified meningiomas. Preliminary 1/T1 profiles for pure CaHA and a single high-field 1/T2 value also are reported. RESULTS: The ranges of dry weights and of low-field 1/T1 values were twice as large for calcified as for noncalcified meningiomas. No correlation was found between low-field 1/T1 and either histologic subtype or dry weight. Mild calcification produced the highest low-field 1/T1 values; the most heavily calcified tumor had slightly increased low-field 1/T1. Calcium hydroxyapatite increases low-field 1/T1 significantly but not high-field 1/T1; high-field 1/T2 is large. For calcified hemorrhagic meningiomas, increases in both low-field and high-field 1/T1 were seen. CONCLUSION: For mild calcification, MRI signal voids result from an increased high-field 1/T2; for heavier calcification, reduced proton density (from excluded water) becomes of increasing importance. Cellular CaHA appears to brighten the signal in T1-weighted MRI in the presence of hemorrhage.

Adolescent↗
PubMed1982

CT features of calcification in abdominal neuroblastoma.

The plan radiographs and computed tomography (CT) scans of 12 children with abdominal neuroblastoma were reviewed to evaluate the incidence and shape of calcification in the tumor. Calcifications were detected in 7 cases by plain radiographs and in 10 by CT. Small dotted and thin ring calcifications were better shown by CT. Ring calcification does not appear to be as rare as has been reported. It is emphasized that all ring calcifications in the vicinity of adrenal glands are not benign.

Abdominal Neoplasms↗
PubMedDate not supplied

Dual kV CT to detect calcification in solitary pulmonary nodule.

OBJECTIVE: At the high kVp values used in CT scanning, almost all interactions in soft tissues occur by Compton scattering. By lowering the kVp close to the k-edge of calcium, beam attenuation by calcium will be greater and will be reflected as an increase in density reading (DR). The presence of calcification in solitary pulmonary nodules (SPNs), and thus an implied benign etiology, is currently being diagnosed on CT by using reference phantoms. We explored the possibility of utilizing low kVp (i.e., 80 kVp) to detect the presence of such calcification in SPNs, thus obviating the need for expensive and cumbersome reference phantoms. MATERIALS AND METHODS: We first tested this phenomenon of photoelectric interaction by CT and its effect on DRs by scanning various dilutions of calcium bicarbonate solution at the standard 140 kVp and at a lower, 80 kVp, setting. After confirming the hypothesis, we conducted a prospective clinical study of 27 consecutive SPNs and scanned them at 140 and 80 kVp to detect the presence of calcification by measuring their DRs at both kVp values. RESULTS: All calcium solutions showed an increase in DR on the 80 kVp scan. Of the 27 nodules, 11 (41%) showed an increase in DR, suggesting the presence of calcification: 10 (91%) were benign, and 1 (9%) was malignant. CONCLUSION: Our study demonstrates that dual kVp CT could be reliably used to identify calcifications in SPNs, very similar to the use of the reference phantoms currently being applied for the purpose.

Calcinosis↗
PubMed1995

Progression and regression by verapamil of vitamin D3-induced calcific medial degeneration in coronary arteries of rats.

Vitamin D3-induced mural calcification represents an animal model for investigating experimental calcium (Ca) overload and calcification of arterial walls. In this study, long-term progression of calcific degeneration in coronary arteries of rats after one intoxication with vitamin D3 was examined, as well as possible regression of preestablished mural Ca overload with the Ca antagonist verapamil. Sprague-Dawley rats were treated with one intramuscular (i.m.) overdose of vitamin D3 [300,000 IU/kg body weight (b.w.)]. Oral verapamil therapy (100 mg/kg/day b.w. for 24 weeks) was initiated 14 days after the vitamin D3 intoxication. Arteriosclerotic alterations were verified by microchemical analyses of tissue Ca and of cholesterol contents with atomic absorption spectroscopy (special graphite tube technique) and gas chromatography, respectively, and by standard histological techniques. Serum lipids were determined by sequential ultracentrifugation. Between week 3 and week 26 after the vitamin D3 injection, a progressive Ca incorporation from 448.8 +/- 110 to 1,310 +/- 166.3% of control values (i.e., coronary Ca content in 32-week-old untreated control rats = 100%) was observed, associated with calcific morphological lesions, and reactive intimal plaque formation. Verapamil prevented this progression and induced a regression of preestablished mural Ca overload. Therefore, the coronary Ca content after 24 weeks of verapamil treatment amounted to only 146.3 +/- 53.8% of controls. The data indicate that an initial calcific lesion of coronary arteries may serve as crystallization nucleus for advancing Ca overload and morphological alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The functional significance of calcification of coronary arteries as detected on CT.

We evaluated the coronary arteries on computed tomography (CT) scans of the chest and on coronary angiograms of 27 patients who underwent both studies. We related the presence or absence of coronary artery calcification on CT to percentage stenosis on angiogram. For the left anterior descending artery (LAD), the likelihood of calcification rose proportionately with degree of stenosis; this was less true for the circumflex, and not true for the right coronary artery (RCA). The sensitivity of CT in detecting coronary artery calcification in patients with angiographic criteria of significant coronary artery disease (CAD) was 78% for the LAD, 63% for the circumflex, and 16% for the RCA. Specificities were 78%, 80%, and 100%, and positive predictive values were 88%, 83%, and 100%. The high positive predictive values suggest that coronary artery calcification diagnosed by chest CT has a high correlation with clinically significant CAD. Therefore, when we detect such calcification in a patient without documented heart disease, we suggest that a cardiac workup is indicated.

Calcinosis↗