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Crystals and calcification patterns in two lymph node calcifications.

Two calcified lymph nodes from the submandibular and neck regions, were studied by micro-radiography, X-ray micro-diffraction and X-ray micro-analysis. The submandibular specimen showed a conglomerate texture of small blocks which seemed to reflect the lobular structure of the lymph node. The degree of calcification of these blocks varied from one location to another. The neck specimen was composed of several islets surrounded by soft tissues. The main islet showed a central X-ray translucent region and outer calcified layers which could be subdivided into 2 types; those with spherulitic calcification and those with smooth calcification. In the submandibular specimen, well crystallized apatite was found, sometimes together with a minor amount of whitlockite. In the neck specimen, isolated and well-crystallized whitlockite was found most frequently in the regions of spherulitic calcification. The occurrence of whitlockite in both specimens was attributed to the sporadic distribution of magnesium, as revealed by X-ray micro-analysis.

Calcinosis↗

Calcification of the ductus venosus: a cause of right upper quadrant calcification in the newborn.

The authors report three cases of ductus venosus calcification as an additional cause of vascular liver calcification in the newborn. All three infants had umbilical venous catheters. The calcification may be caused by extravasated fluids given through the catheter or by local trauma due to catheter insertion. An obliquely oriented, paravertebral "tram-track" calcification in the right upper quadrant, particularly in a premature infant with a history of umbilical venous catheterization, should suggest the diagnosis of calcified ductus venosus.

Calcinosis↗

Mitral annular calcification and aortic valve calcification may help in predicting significant coronary artery disease.

Mitral annular calcification (MAC) and aortic valve calcification (AVC) are manifestations of atherosclerosis. To determine whether mitral annular calcification and aortic valve calcification detected by transthoracic echocardiography (TTE) might help in predicting significant coronary artery disease (CAD), 123 patients with significant CAD and 93 patients without CAD detected by coronary angiography were investigated. MAC and AVC identified CAD with a sensitivity and specificity of 60.2%, 55.9% and 74.8%, 52.7%, respectively, and with a negative and a positive predictive values of 51.5%, 64.3% and 61.3% and 67.6%, respectively. The positive predictive value of MAC was greater than gender, hypertension, and hypercholesterolemia. AVC showed a positive predictive value greater than gender, hypertension, family history, and hypercholesterolemia. The negative predictive values of MAC and AVC for CAD were greater than those of all risk factors except diabetes mellitus. In conclusion, presence of MAC and AVC on TTE may help in predicting CAD and should be added to conventional risk factors. Absence of MVC and AVC is a stronger predictor for absence of CAD than all conventional risk factors, except diabetes mellitus. Patients with MAC and AVC should be taken into consideration for the presence of significant CAD and thereby for diagnostic and therapeutic interventions in order to improve the prognosis.

Adult↗

[Preparation of vascular calcification in vivo and vascular smooth muscle cell calcification in vitro of rats].

OBJECTIVE: To investigate simple, economical, stable and efficient methods of in vivo and in vitro cardiovascular calcification models in rats. METHODS: Rats received Vitamin D(3) (300 000 U/kg, i.m.) and nicotine (25 mg/kg, 5 mL/kg in peanut oil, p.o.) at 8 a.m. on day 1. The nicotine administration was repeated at 6 p.m. Rats in control group received an injection of normal saline (i.m.) and two gavages of medium oil. All of the rats were then allowed to recover for 4 weeks and given standard rodent chow. After the measurement of cardiac function the rats were sacrificed and the calcium content in myocardium and aorta were measured. Von Kossa staining was used to detect the deposit of calcium in myocardium and aorta. Cultured smooth muscle cell(SMC) derived from rat thoracic aorta was treated with beta-glycerophosphate for 14 days, then the calcium content and deposit were measured. RESULTS: Compared with control group, the rats with cardiovascular calcification showed a lower body weight, The ratio of left heart to body weight, myocardial and aortic calcium content were increased respectively. Alkaline phosphatases activity in calcified myocardium and aorta were increased respectively, compared with the control. The values of animal mean blood pressure (MBP), heart rate (HR) and left ventricle end-distolic pressure (LVEDP) showed no significant alteration (P>0.05) in vitamin D3 plus nicotine (VDN) group. The values of +LV dp/dt(max) and -LV dp/dtmax were significantly lower in VDN group (P<0.05 and P<0.01, respectively). In calcified vascular smooth muscle cells(VSMCs), von Kossa staining for calcification, showed positive staining as black/brown areas within the main, large, nodular structures as shown in extracellular matrix and cytoplasma. The content of calcium, (45)Ca(2+) uptake and alkaline phosphatase (ALP) activity in calcified VSMCs were increased (all P<0.01), respectively, compared with that of the control. CONCLUSION: These methods can be used to produce calcification models in vivo and in vitro, which save money and time and are easy to manipulate.

Animals↗

Calcification in breast arteries. The frequency and severity of arterial calcification in female breast tissue without malignant changes.

94 breast specimens without malignant changes, from women 30-89 years of age, were investigated for arterial calcification, graded in three degrees. In 40 specimens calcification of the vessels was found. The frequency of calcified vessels and the three grades of calcification varied with age, grade I predominating in the medium age-groups and grade III dominating in the oldest age-groups. It is concluded that calcification of breast arteries is a frequent degenerative age-related change, most severe in the oldest age-groups.

Adult↗

[Angiographic study of stenosis and calcification of coronary vessels in long-term dialysis patients: examination of risk factors for coronary calcification].

Coronary atherosclerosis and calcification score were assessed angiographically in 30 uremic patients receiving dialysis (8 patients with diabetes mellitus [DM dialysis group] and 22 patients without DM [non-DM dialysis group] who were suspected of having coronary artery disease because of their clinical symptoms and electrocardiographic findings. Thirty non-uremic subjects (11 with DM and 19 without DM) served as controls. Twelve dialysis patients (40%) did not have significant coronary artery disease, and the rate of significant coronary artery disease in dialysis patients overall was less than that in the control subjects. The calcification score of dialysis patients was significantly higher than that of the control patients (P < 0.0001), and also scores of the non-DM dialysis group and the DM dialysis group were higher than those of each group of control subjects. The scores were significantly correlated with the duration of dialysis in uremic patients as a group (r = 0.52; P < 0.01) and the non-DM dialysis group (r = 0.70; P < 0.01), but were not correlated with the duration of dialysis in the DM dialysis group. The scores were correlated with serum phosphate concentration, but not with serum calcium concentration, calcium phosphate product, alkaline phosphatase levels total cholesterol or age. Calcification scores were extremely high (> 21) in six uremic patients who had high serum c-terminal parathyroid hormone concentrations. These findings indicate that serum phosphate concentration, serum c-terminal parathyroid hormone concentration, and the duration of dialysis are closely associated with coronary calcification in long-term dialysis patients.

Adult↗

Cellular and matrix changes before and at the time of calcification in the growth plate studied in vitro: arrest of type X collagen synthesis and net loss of collagen when calcification is initiated.

To understand the growth, maturation, and regulation of growth plate chondrocytes, it is necessary to isolate the different chondrocytes into distinct subpopulations of maturational development. Five subpopulations (A-E) of bovine fetal growth plate chondrocytes were separated by discontinuous gradient centrifugation. Four subpopulations (B, C, D, and E, from low to high density) with good viability were cultured at high density in microwells for up to 30 days. They all established an extensive extracellular matrix composed of proteoglycan and collagen. The largest and last dense cells in subpopulation B were the first to synthesize (at days 5-6) type X collagen and to calcify this matrix. Matrix calcification (formation of hydroxyapatite in the presence of sodium beta-glycerophosphate) always followed the initiation of type X synthesis. All the other subpopulations synthesized type X collagen and calcified their extracellular matrix. Although these events occurred in the same order, they were delayed according to the order of increasing cell size. These observations indicate that these subpopulations represent different stages in cellular maturation that lead to expression of the hypertrophic phenotype. Once mineral formation was well established, there was an increase in the matrix content of the C-propeptide of type II collagen (which is known to bind to hydroxyapatite and accumulate in calcifying extracellular matrix). This was accompanied by a reduction in the total collagen content, which accompanied an abrupt reduction in type X collagen synthesis, whereas type II collagen synthesis was largely maintained. These reductions in collagen content and type II collagen synthesis were not observed in the absence of calcification (beta-glycerophosphate omitted from culture). This new culture system recreates many of the sequential cellular and extracellular changes exhibited in situ during the development of the physis and provides new information about cellular and extracellular matrix changes that occur before and at the time of calcification.

Absorptiometry, Photon↗

Experimental calcification of HEMA-based hydrogels in the presence of albumin and a comparison to the in vivo calcification.

The precipitation patterns and characteristics of calcium phosphate (CaP) phases deposited on HEMA-based hydrogels upon incubation in simulated body fluid (SBF-2) containing a protein (human serum albumin) have been investigated in relation to the calcification in an organic-free medium (SBF-1) and to that occurring after subcutaneous implantation in rats. In SBF-2, the deposits occurred exclusively as a peripheral layer on the surface of the hydrogels and consisted mainly of "precipitated hydroxyapatite", a species deficient in calcium and hydroxyl ions, similarly to the deposits formed on the implanted hydrogels, where the deposited layer was thicker. In SBF-1, the deposits were mainly of brushite type. There was no evidence that albumin penetrated the interstices of hydrogels. As the X-ray diffraction patterns of the CaP deposits generated in SBF-2 showed a similar nature with those formed on the implanted hydrogel, it was concluded that the calcification in SBF-2 can mimic to a reliable extent the calcification process taking place in a biological environment.

Animals↗

Effect of type 1 diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study.

The objective of this is study was to examine whether estimated insulin resistance and insulin resistance-related factors are associated with coronary artery calcification (CAC) in 1,420 asymptomatic participants in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. A total of 656 patients with type 1 diabetes and 764 control subjects aged 20-55 years were examined. CAC was assessed by electron-beam computed tomography. Insulin resistance was computed with linear regression based on an equation previously validated in clamp studies on type 1 diabetic adults. Insulin resistance was associated with CAC (OR 1.6 in type 1 diabetes and 1.4 in control subjects, P < 0.001), independent of coronary artery disease risk factors. There was a male excess of CAC in control subjects (OR 2.7, adjusted for age, smoking, and LDL and HDL cholesterol levels) and in type 1 diabetic patients (OR 2.2, adjusted for the same factors and diabetes duration). After adjusting for insulin resistance, the CAC male excess in diabetic patients decreased from OR 2.2 (P < 0.001) to 1.8 (P = 0.04). After adjustment for waist-to-hip ratio, waist circumference, or visceral fat, the gender difference in CAC was not significant in diabetic subjects. In conclusion, gender differences in insulin resistance-associated fat distribution may explain why type 1 diabetes increases coronary calcification in women relatively more than in men.

Adult↗

Calcification in an intramyocardial mass lesion: isolated calcification of an accessory papillary muscle in a patient with mitral prolapse.

Cardiac catheterization in a 50-year-old male with mitral leaflet prolapsed revealed a filling defect with calcification in the high posterolateral wall. At surgery, the lesion was found to be a calcified accessory papillary muscle with thickened, calcified chordae to the posterior leaflet. The calcification and fibrosis were felt to be due to friction lesions between elongated chordae and the endocardium. Intracardiac calcification in mitral leaflet prolapsed may suggest calcified mitral apparatus.

Calcinosis↗

Familial calcification of aorta and calcific aortic valve disease associated with immunologic abnormalities.

We report three patients of the same family with linear calcification of the ascending aorta, severe calcific mixed aortic valve disease associated with increased levels of globulins, lambda-chain gammopathy, an increased T4/T8 lymphocyte ratio, and other immunologic abnormalities. None of the patients had syphilis, atherosclerosis, abnormalities of calcium or phosphorus metabolism, lymphadenopathy, or other systemic diseases. It is postulated that these cases and some previously reported in the literature as idiopathic represent a distinct pathologic entity, familial or sporadic, in which localized vascular and valvular calcific disease is associated with an underlying immunologic disorder or autoimmune process.

Adult↗

Association between progression of aortic valve calcification and coronary calcification: assessment by electron beam tomography.

RATIONALE AND OBJECTIVES: It has been demonstrated that aortic valve calcification (AVC) shares many similarities with coronary atherosclerosis, including risk factors and pathologic characteristics. We sought to examine the relationship of AVC to coronary artery calcification (CC), to assess whether similar risk factors affect the process in a similar way. MATERIALS AND METHODS: The study included 620 asymptomatic persons (513 men and 107 women, mean age 59 years range [30-82]) who underwent two consecutive electron beam tomography (EBT) scans at least 1 year apart (mean 3.3 years). Calcification scores were obtained by summation of Agatston and volumetric scores. Stabilization of calcium was defined as no increase in score per year or positive percent change in score </=1%/year. Progression was defined as a positive percent change in score >1%/year. Of 106 with AVC, 105 (99%) had CC. Sixty-five patients had an AVC >10 on initial scan, and 50 (77%) demonstrated progression on the follow-up scan. Of 394 participants with CC >10 on initial scan, follow-up scans showed CC stabilization in 64 (16.2%) and CC progression in 330 (83.8%). Patients with AVC were significantly older than those with only CC (64.5 versus 56.5 years, P < .0001). The average age of the patient with AVC was 7 years older than the average age with CC. AVC (by volumetric score) progressed more rapidly in patients with diabetes (P = .036) and smoking (P = .042) than those without. RESULTS: We found no difference in the degree of change in the CC scores (by Agatston or volumetric methods) over time between men and women, or in any baseline cardiac risk factor (P > .05 for all measures). In 65 patients with both AVC and CC >10, there was a significant association between progression of AVC and CC (P = .047); the absolute rate of change of AVC was 24.5 +/- 43.2 %/year, and CC was 28.0 +/- 49.1 %/year. CONCLUSION: Virtually all patients with AVC had CC, potentially explaining the coronary risk associated with AVC. There is substantially parallel development between rates of progression of EBT-assessed AVC and CC.

Adult↗

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age < or =65 years old.

OBJECTIVES: We examined the hypothesis that mitral annulus calcification (MAC), aortic valve sclerosis (AVS) and aortic root calcification (ARC) are associated with coronary artery disease (CAD) in subjects age < or =65 years. BACKGROUND: Mitral annulus calcification, AVS and ARC frequently coexist and are associated with coronary risk factors and CAD in the elderly. METHODS: We studied 338 subjects age < or =65 years who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography (SPECT) and a two-dimensional transthoracic echocardiogram for other indications. The association of MAC, AVS and ARC with abnormal SPECT was evaluated by using chi-square analyses and logistic regression analyses. RESULTS: Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (> or =2) calcium (or sclerosis) deposits with diabetes or multiple (> or =2) coronary risk factors were significantly associated with abnormal SPECT in women age < or =55 years old (odds ratio [OR], 20.00), in women age >55 years old (OR, 10.00) and in men age < or =55 years old (OR, 5.55). Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age < or =55 years (p < 0.05) and the total group of subjects (p < 0.01). CONCLUSIONS: When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men < or =55 years old and women.

Aged↗

Identification and characterization of vascular calcification-associated factor, a novel gene upregulated during vascular calcification in vitro and in vivo.

OBJECTIVE: Vascular calcification, with its increasing clinical sequelae, presents an important and unresolved dilemma in cardiac and vascular practice. We aimed to identify molecules involved in this process to develop strategies for treatment or prevention. METHODS AND RESULTS: Using subtractive hybridization, a novel cDNA, designated vascular calcification-associated factor (VCAF), has been isolated from a bovine retinal pericyte cDNA library generated during the differentiation and mineralization of these cells in vitro. RNA ligase-mediated rapid amplification of cDNA ends was used to compile the 740-bp bovine cDNA sequence. Database searching reveals that VCAF has novel nucleotide/amino acid sequences. RNA analysis confirms that VCAF is upregulated in mineralized pericytes and is present in human calcified arteries but not noncalcified arteries. Protein analysis using a VCAF antibody confirms the presence of an 18-kDa protein in calcified nodules but not in confluent pericytes. Adenoviral antisense VCAF gene delivery reduces VCAF protein levels and accelerates pericyte differentiation compared with controls. CONCLUSIONS: We demonstrate the isolation of a novel gene, VCAF, which is upregulated during vascular calcification in vitro and in vivo. Antisense VCAF gene delivery accelerates pericyte differentiation, implicating a role for VCAF in this clinically significant pathological process.

Adenoviridae↗

Vascular ossification-calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis-calcific uremic arteriolopathy: the emerging role of sodium thiosulfate.

BACKGROUND: Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling). The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall. RESULTS: The pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician-researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare) is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisoning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication. CONCLUSION: A discussion of sodium thiosulfate's dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications.

Animals↗

Spherical liquefaction necrosis of mitral annular calcification in a chronic dialysis patient--liquefaction necrosis of mitral annular calcification.

A 60-year-old woman on chronic dialysis consulted our department for closer examination of transient atrial fibrillation and a mitral regurgitant murmur. Echocardiography revealed a left atrial abnormal dense echogenic spherical mass, the diameter of which was 2 cm. She died of cerebral bleeding 3 months later. At autopsy, the submitral mass-like structure consisted of light-gray pasty material, which was liquefaction necrosis of a mitral annular calcification. These findings were different from those of the so-called mitral annular calcification found in the elderly or in chronic renal failure patients. The existence of such calcification must be kept in mind and not be mistaken for cardiac tumor.

Atrial Fibrillation↗

Pleural calcification: a type of "metastatic calcification" in chronic renal failure.

Pulmonary calcifications associated with chronic renal failure are rare conditions. However, a few such cases have been reported in the literature, and they were regarded as a sign of secondary hyperparathyroidism. Pleural calcification induced by secondary hyperparathyroidism has not been reported in the literature. We report four cases of slow-growing pleural calcification which are considered to have been induced by hyperparathyroidism, in patients undergoing maintenance haemodialysis for chronic renal failure. CT scan was useful for the detection of calcified lesions in the pleura.

Adult↗

Cartilage calcification: an ultrastructural, histochemical, and analytical x-ray microprobe study of the zone of calcification in the normal avian epiphyseal growth plate.

Sections from the zone of calcification of ruthenium red-fixed normal avian epiphyseal growth plates were analyzed by various morphological (histochemical) and analytical techniques. Calcium and phosphorus were identified in the chondrocyte pericellular rim, the uncalcified extracellular (territorial) matrix, and in both the peripheral and central aspects of the calcified accumulations within extracellular matrix. Cartilage proteoglycan, as determined by ruthenium binding, positive staining with acidic phosphotungstic acid, and the X-ray spectroscopic detection of sulfur, was identified in the same four zones. Thus, it appears that proteoglycans, in some form, are indeed retained at sites of biological calcification. Additionally, these macromolecules, synthesized in chondrocytes, may be involved in extracellular calcium translocation.

Animals↗