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PubMed2002

Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo.

Osteopontin (OPN) is abundantly expressed in human calcified arteries. To examine the role of OPN in vascular calcification, OPN mutant mice were crossed with matrix Gla protein (MGP) mutant mice. Mice deficient in MGP alone (MGP(-/-) OPN(+/+)) showed calcification of their arteries as early as 2 weeks (wk) after birth (0.33 +/- 0.01 mmol/g dry weight), and the expression of OPN in the calcified arteries was greatly up-regulated compared with MGP wild-types. OPN accumulated adjacent to the mineral and colocalized to surrounding cells in the calcified media. Cells synthesizing OPN lacked smooth muscle (SM) lineage markers, SM alpha-actin and SM22alpha. However, most of them were not macrophages. Importantly, mice deficient in both MGP and OPN had twice as much arterial calcification as MGP(-/-) OPN(+/+) at 2 wk, and over 3 times as much at 4 wk, suggesting an inhibitory effect of OPN in vascular calcification. Moreover, these mice died significantly earlier (4.4 +/- 0.2 wk) than MGP(-/-) OPN(+/+) counterparts (6.6 +/- 1.0 wk). The cause of death in these animals was found to be vascular rupture followed by hemorrhage, most likely due to enhanced calcification. These studies are the first to demonstrate a role for OPN as an inducible inhibitor of ectopic calcification in vivo.

Animals↗
PubMed2002

Calcific trochanteric bursitis: resolution of calcifications and clinical remission with non-invasive treatment. A case report.

Calcific trochanteric bursitis, a common regional pain syndrome, is characterized by chronic, intermittent aching pain over the lateral aspect of the hip and limitation of function. Effective treatment is invasive, including infiltration therapy and surgical intervention. The therapeutic effects of conservative treatment modalities have not been proven. A 59-year-old woman presented at the department of physical medicine and rehabilitation with a 2-year history of pain in the right hip. She had been treated with several agents such as glucocorticoids and local anesthetics (via injection) for two years, but without success. Physical examination revealed the clinical diagnosis of bursitis trochanterica. Radiographic findings showed calcified rounded masses measuring about 1.5 cm in diameter around the greater trochanter; a calcific bursitis trochanterica was diagnosed. The patient presented for conservative treatment in order to avoid surgical intervention for removing the calcification and the bursal sac. A non-invasive treatment regimen including intensive pulsed ultrasound therapy, physiotherapy and iontophoresis was started. The conservative treatment led to a remission of both, symptoms as well as radiographic findings, which revealed complete resolution of calcifications. This case report shows that, in cases of calcific trochanteric bursitis (including those with extensive calcifications), a non-invasive conservative treatment regimen including intensive high-dosed pulsed ultrasound therapy should be attempted before more invasive treatment (injections, surgery) is considered.

Bursitis↗
PubMed1975

[Calcification in gliomas: first report with special reference to roentgenological calcification (author's transl)].

The mechanism and the clinical significance of calcium deposits in glioma have been still obscure. Excluding pinealomas, 221 histologically proven intracranial gliomas were studied. The presence of roentgenological calcification in 27 of the authers' series represented an incidence of 12 percent. The incidence of roentgenological calcification in various types of glioma were as follows: astrocytoma grades 1 & 2-15%, astrocytoma grades 3 & 4-7%, medulloblastoma-5%, ependymoma-17%, oligodendrogioma-60%, and choroid plexus papilloma-25%. There was no characteristic relationship between the incidence of calcification and the age distribution. One exception was noted that in astrocytoma grades 1 & 2 the incidence of roentgenological calcification tended to be higher in younger patients than in older patients. The percentage of calcified tumors in both sexes was the same. In astrocytoma and ependymoma the incidence of roentgenological calcification was far greater in the supratentorial tumor than in the infratentorial tumor. According to their roentgenological appearance, calcified tumors were separated into four groups, but any specific appearance could not be claimed for any particular type of glial tumors. Only in astrocytoma both the duration of symptoms and the postoperative survival time of the calcified cases were longer than those of the uncalcified. But in other types of glioma there were no significant differences in the postoperative survival time between the calcified cases and the uncalcified ones. In 5 cases of astrocytomas the calcium deposits did not exist on preoperative radiographs, which were found postoperatively after chemotherapy and/or radiotherapy. In conclusion, it is not the histological type but the duration of the clinical course that plays more important role in calcification of gliomas.

Adolescent↗
PubMed1978

Effect of hydrochlorothiazide on urine saturation with brushite, in vitro collagen calcification by urine, and urinary inhibitors of collagen calcification.

To clarify further the beneficial effect of thiazide diuretics on recurrent calcium nephrolithiasis, the effect of short-term hydrochlorothiazide therapy on urine saturation with brushite (CaHPO(4).2H(2)O), in vitro collagen calcification by urine, and urinary inhibitors of calcification was studied.In 22 patients with idiopathic calcium oxalate/phosphate stones the urine calcium excretion decreased, the urine magnesium excretion increased and the urine magnesium/calcium ratio increased significantly (P < 0.001) during hydrochlorothiazide therapy. Supersaturation of the urine with brushite, which was present in 19 of the 22 patients, was reduced significantly (P < 0.001) in all during thiazide therapy, and to the undersaturated range in 16. The ability of urine to calcify collagen in vitro also decreased significantly (P < 0.001) during thiazide therapy, a change that correlated significantly (r = 0.4513, P < 0.05) with the decrease in brushite saturation. The concentration of urinary inhibitors of calcification, as determined with an in vitro collagen calcification system, was decreased significantly (P < 0.01) by thiazide therapy.It was concluded that, in addition to decreasing urine calcium excretion and increasing urine magnesium excretion, thiazide diuretics decrease the urinary brushite saturation and thus may prevent spontaneous nucleation or crystal growth, or both, of calcium phosphate. The ability of thiazides to decrease collagen calcification in vitro suggests that they may also prevent crystal growth on a nidus of organic matrix. Thiazides do not appear to act by increasing the excretion of urinary inhibitors of calcification.

Adult↗
PubMed1992

Prevention of tissue calcification on bioprosthetic heart valve by using epoxy compounds: a study of calcification tests in vitro and in vivo.

Calcification is the principal cause of the clinical failures of the bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. In this paper, we compared the calcification on various types of bovine pericardiums pretreated with two hydrophilic epoxy compounds adding GA post-treatment (EP 1 and EP 2), glutaraldehyde (GA)- and nontreated pericardium (Fresh), respectively, by in vitro and in vivo tests. Significant decrease of calcification was found by pretreatment with both epoxy compounds rather than with glutaraldehyde: 0.250 +/- 0.001 (Fresh), 0.276 +/- 0.058 (EP 1), 0.302 +/- 0.071 (EP 2), and 0.478 +/- 0.172 (GA) micrograms (Ca)/mg (dried tissue), respectively, after 20 days dipping in a simulating serum solution in vitro; 115.13 +/- 60.11 (Fresh), 129.84 +/- 51.08 (EP 1), 167.39 +/- 20.81 (EP 2), and 205.19 +/- 16.86 (GA) micrograms/mg, respectively, after 3 months subcutaneous implantation in rabbits. The in vitro method for evaluating calcification designed by us gave the similar order among four samples with that obtained by in vivo test. Because the bovine pericardium pretreated with the epoxy compounds adding GA post-treatment possesses the greater tenacity than that pretreated only with epoxy compounds or GA, meanwhile the calcification is also significantly decreased with this pretreatment, it may be expected that the bovine pericardium with this pretreatment will have the greater anticalcification and durability in dynamic stress.

Animals↗
PubMed1984

Calcific pancreatitis: calcification patterns and pancreatogram correlations.

The abdominal radiographs of 74 patients with calcific pancreatitis were reviewed to assess the distribution, density and patterns of calcification. These characteristics were compared with the results of endoscopic retrograde cholangiopancreatography and ultrasonography. There was a decreasing gradient of calcification from head to tail in most patients. Foci of calcification greater than 5 mm in diameter were almost always associated with pancreatic duct obstruction. Endoscopic retrograde cholangiopancreatography did not provide additional diagnostic information and is unnecessary in calcific pancreatitis except when a precise map is required before operation.

Adolescent↗
PubMed2002

Cerebral, myocardial and cutaneous ischemic necrosis associated with calcific emboli from aortic and mitral valve calcification in a patient with end-stage renal disease.

We report the case of a 57-year-old diabetic male with chronic renal failure who developed secondary hyperparathyroidism and calcification of mitral and aortic valves and interatrial septum. Multiple ischemic lesions developed in the skin of hands, feet and penis, and in the brain, and these were presumed to be due to septic emboli from cardiac valvular infective endocarditis. Multiple blood cultures were negative, however, and despite antibiotic therapy the patient expired. Autopsy (limited to trunk) demonstrated multiple calcific emboli in the heart and spleen, apparently derived from the prominent calcific deformities in the aortic and mitral valves. These were associated with acute and organizing myocardial infarcts and acute splenic infarcts, suggesting that the multiple ischemic lesions in the brain were also due to calcific emboli. A possible contributory component of infective endocarditis, however, was indicated by postmortem cultures of aortic and mitral valves positive for Enterococcus faecium. Calcific embolism is a rarely recognized but potentially lethal complication of end-stage renal disease, and the clinical diagnosis and the preventive therapeutic options for the control of the product of calcium and phosphate and/or parathyroidectomy should be considered.

Aortic Valve↗
PubMed2001

Localizational alterations of calcium, phosphorus, and calcification-related organics such as proteoglycans and alkaline phosphatase during bone calcification.

To further approach the mechanisms of bone calcification, embryonic rat calvariae were observed at electron microscopic level by the means of fine structures and various cytochemical localizations, including nonspecific proteoglycan (PG) stained by cuprolinic blue (CB), decorin, chondroitin sulfate, hyaluronan, and alkaline phosphatase (ALP), as well as the elemental mapping of calcium (Ca) and phosphorus (P) by energy-filtering transmission electron microscopy (EFTEM). In the calvariae, calcification advanced as the distance from osteoblasts increased. Closer to the osteoblasts, the osteoid was marked by an abundance of CB-positive PGs around collagen fibrils. After crystallization within matrix vesicles, calcified nodules formed and expanded, creating a coherent calcified matrix. The sizes of CB-positive PG-like structures diminished as calcification proceeded. Although small CB-positive structures were accumulated in early stage-calcified nodules, they were localized along the periphery of larger calcified nodules. Cytochemical tests for decorin, chondroitin sulfate, and hyaluronan determined their presence in the areas around collagen fibrils of the osteoid, as well as in and around calcified nodules, whereas ALP was found in the matrix vesicles, as well as in and around the calcified nodules. Ca tended to localize at the PG sites, while P often mapped to the collagen fibril structures, in the uncalcified matrix. In contrast, Ca/P colocalization was visible in and around the calcified nodules, where ALP and smaller CB-positive structures were observed. The difference in the localization patterns of Ca and P in uncalcified areas may limit the local [Ca2+][PO4(3-)] product, leading to the general inhibition of hydroxyapatite crystallization. The downsizing of CB-positive structures suggested enzymatic fragmentation of PGs. Such structural alterations would contribute to the preservation and transport of calcium. ALP possesses the ability to boost local phosphate anion concentration. Therefore, structurally altered PGs and ALP may cooperate in Ca/P colocalization, thus promoting bone calcification.

Alkaline Phosphatase↗
PubMed1996

Calcific tenosynovitis associated with calcific myonecrosis of the leg: imaging features.

The findings with histologically proven calcific tenosynovitis of the tibialis anterior tendon associated with calcific myonecrosis are described. This case emphasizes the typical appearance of this unusual relationship such as peripheral plaque-like calcifications of the tendon sheath, fluid-calcium levels, presentation as painless mass, and calcification and liquefaction of muscle bundles.

Aged↗
PubMed1987

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↗
PubMed1989

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↗
PubMed1985

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↗
PubMed1996

[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↗
PubMed1994

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↗
PubMed1978

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↗
PubMed1993

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↗
PubMed2001

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↗
PubMed1992

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↗