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Glutaraldehyde treated bovine pericardium: changes in calcification due to vitamins and platelet inhibitors.

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B6, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GABP. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B6, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications.

Animals↗

Aortic medial calcification in progeria-like syndrome.

Aortic medial calcification was investigated in rats in which the progeria-like syndrome (PLS) was evoked by administering dihydrotachysterol. In 35 experimental rats and 15 controls, calcification was studied morphologically by light and electron microscopy, and by enzyme histochemistry. Body weight, food intake and serum calcium levels were also determined. Calcification occurred along and on the elastic lamellae in association with the accumulation of ground substance. In the smooth-muscle cells surrounding the calcified foci, the activities of various lysosomal enzymes increased concomitantly with a tendency toward transformation of smooth-muscle cells to a modified form. From these observations, the role of ground-substance formation by smooth-muscle cells is postulated, and participation in the catabolism of ground substance by the lysosomal enzymes of these cells is suggested. It appears the increased activity of adenosine monophosphatase should be linked to the calcification. The etiology of weight loss, skin manifestations and aortic calcification in PLS rats seems to be different from that in human progeric diseases. Therefore, the PLS rat should not be readily accepted as an animal model for the study of progeric diseases.

Acid Phosphatase↗

Mitral valve replacement in the presence of severe valvular and annular calcification.

Degenerative and rheumatic mitral valve disease are associated with calcification of the annulus, leaflets, and subvalvular mechanism. Surgical treatment is greatly affected by the presence of such calcification, which frequently precludes successful repair, mandating valve replacement. Dense calcification of the posterior leaflet, annulus, and chordae can cause great difficulty in the insertion of a prosthetic device, and is associated with a high frequency of technical complications. We have devised a technique of replacing the mitral valve in the face of such severe calcification, which allows the surgeon to safely insert a single disc mechanical prosthetic valve, avoiding the calcification completely. A large Teflon felt collar precludes the need to place any sutures through the posterior valve leaflet. Successful early experience with five patients, exhibiting both degenerative and rheumatic disease, is described.

Aged↗

Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats.

AIM: To investigate the role of the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H2S) pathway in vascular calcification in vivo. METHODS: A rat vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN). The amount of CSE and osteopontin (OPN) mRNA was determined by using semi-quantitative reverse-transcription polymerase chain reaction. The calcium content, 45Ca2+ accumulation and alkaline phosphatase (ALP) activity were measured. H2S production and CSE activity were measured. RESULTS: von Kossa staining produced strong positive black/brown staining in areas among the elastic fibers of the medial layer in the calcified aorta. The calcium content, 45Ca2+ accumulation and ALP activity in calcified arteries increased by 6.77-, 1.42-, and 1.87-fold, respectively, compared with controls. The expression of the OPN gene was upregulated (P<0.01). Expression of the CSE gene was downregulated. However, calcium content, 45Ca2+ uptake and ALP activity in the VDN plus NaHS group was lower than that in the VDN group. The content of calcium and 45Ca2+ accumulation and activity of ALP in the aorta were 34.8%, 40.75% and 63.5% lower in the low-dosage NaHS group than in the VDN group, respectively (P<0.01), and the calcium content and deposition of 45Ca2+ and activity of ALP was 83.9%, 37.8 % and 46.2% lower in the aorta in the high-dosage NaHS group than in the VDN group, respectively (P<0.01). The expression of the OPN gene was downregulated. CONCLUSION: The production of H2S, and CSE activity were decreased and CSE gene expression was downregulated in rats with vascular calcification. H2S can ameliorate vascular calcification, suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.

Animals↗

Removal of arterial wall calcifications in CT angiography by local subtraction.

CT Angiography (CTA) is an established technique for the minimally invasive imaging of arteries. The technique of maximum intensity projection (MIP) is often used to get a comprehensive overview of the vascular anatomy. On a MIP, however, arterial wall calcifications may hinder the visualization of the arterial lumen. These calcifications are in direct contact with the contrast-enhanced blood, which makes removal difficult. We present a local subtraction method for the automatic removal of these calcifications. In our approach a second CT scan has to be made, prior to contrast injection. The calcifications in both scans are registered prior to subtraction to compensate for displacements in between the two scans. Local subtraction results are compared with results obtained by thresholding. The method was tested in a phantom and with data from four patients. The phantom represented an artery with different types of stenosis. Data were used from patients for which CTA of the renal arteries was performed. For two patients the electrocardiogram (ECG) was recorded during the CTA examination, making retrospective cardiac gated reconstructions possible. Both the phantom and the patient study showed that the local subtraction method is capable of removing calcifications and visualizing the residual lumen. In the patient study it appeared that some artifacts remained for higher pitch values. We conclude that the local subtraction method is less subjective and more accurate than thresholding. Best results are obtained by use of a small pitch, at the expense of the volume covered during a single breath hold.

Algorithms↗

Corneal calcification.

Superficial calcification was produced in the normal rabbit cornea by mild irradiation with a carbon dioxide laser. The calcification was entirely extracellular and closely resemnbled that observed in human band keratopathy, which was characterized as hydroxyapatite by x-ray diffraction. The electron-mnicroscopic appearance of calcific spheriules and conglomerates in early cornteal calcification is presented. The calcific spherules arise at the basal plasma membrane surface of the epithelial cells in close relation to their basement membrane.

Animals↗

The incidence of renal calcification in preterm infants.

A total of 79 infants born at less than 32 weeks' gestation were studied with serial renal ultrasound scans to assess the incidence of nephrocalcinosis. Twenty one infants developed renal calcification giving an overall incidence of 26.6% in the study group. Affected infants were significantly smaller (mean (SD) birth weight 940 (323) g) and significantly less mature (mean (SD) gestation 26.9 (1.9) weeks). In 17 patients the calcification was represented by hyperechogenic renal pyramids alone, and in four patients renal calculi were demonstrated. Factors associated with renal calcification included hypophosphataemia, hypercalcaemia, hypercreatininaemia, and prolonged oxygen requirement during the first month of life. Multivariate analysis showed that the strongest clinical indicator of calcification was duration of oxygen treatment. Infants who still required oxygen treatment at 28 days had a 62% chance of developing renal calcification.

England↗

Pineal gland calcification and defective sense of direction.

Calcification of the pineal gland is shown to be closely related to defective sense of direction. In a tricentre prospective study of 750 patients lateral skull radiographs showed that 394 had calcified pineal glands. Sense of direction was assessed by subjective questioning and objective testing and the results noted on a scale of 0-10 (where 10 equals perfect sense of direction). The average score for the 394 patients with pineal gland calcification was 3.7 (range 0-8), whereas the 356 patients without pineal gland calcification had an average score of 7.6 (range 2-10). This difference was highly significant (p less than 0.01). A smaller parallel study in pigeons showed that pineal calcification also leads to a reduction in homing abilities. The findings suggested that the pineal gland plays an important part in directional sense and that damage to the gland, as indicated by calcification, causes defective sense of direction - perhaps by altering the intrinsic intracranial electromagnetic environment and thus affecting the magnetite response mechanism.

Age Factors↗

The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis.

OBJECTIVE: To test the hypothesis that vitamin D receptor polymorphism is associated with calcific aortic valve stenosis. DESIGN: The distribution of one polymorphism of the vitamin D receptor (BsmI B/b) was examined in 100 consecutive patients with calcific valvar aortic stenosis and compared with a control group of 100 patients (paired match for age, sex, and the presence of coronary artery disease from a total of 630 patients without calcified aortic valves). Polymerase chain reaction and restriction fragment length polymorphism were used to determine genotypes. RESULTS: There was a significant difference in vitamin D receptor allele and genotype frequencies between the two groups. The allele B had a higher prevalence in patients with calcific aortic stenosis (B = 0.56, b = 0.44) than in the control cohort (B = 0.40, b = 0.60) (p = 0.001). CONCLUSIONS: There is a significant association of vitamin D receptor polymorphism with calcific aortic valve stenosis. The B allele of the vitamin D receptor is more common in patients with calcific aortic valve stenosis. It now needs to be evaluated whether other genes that control calcium homeostasis are involved in the pathogenesis of this disorder.

Aged↗

Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve.

OBJECTIVE: To study in a rabbit model the expression of endothelial nitric oxide synthase (eNOS) in association with the development of calcification of the aortic valve, and to assess the effects of atorvastatin on eNOS expression, nitrite concentration, and aortic valve calcification. METHODS: Rabbits (n = 48) were treated for three months: 16, forming a control group, were fed a normal diet; 16 were fed a 0.5% (wt/wt) high cholesterol diet; and 16 were fed a 0.5% (wt/wt) cholesterol diet plus atorvastatin (2.5 mg/kg/day). The aortic valves were examined with eNOS immunostains and western blotting. Cholesterol and high sensitivity C reactive protein (hsCRP) concentrations were determined by standard assays. Serum nitrite concentrations were measured with a nitric oxide analyser. eNOS was localised by electron microscopy and immunogold labelling. Calcification in the aortic valve was evaluated by micro-computed tomography (CT). RESULTS: Cholesterol, hsCRP, and aortic valve calcification were increased in the cholesterol fed compared with control animals. Atorvastatin inhibited calcification in the aortic valve as assessed by micro-CT. eNOS protein concentrations were unchanged in the control and cholesterol groups but increased in the atorvastatin treated group. Serum nitrite concentrations were decreased in the hypercholesterolaemic animals and increased in the group treated with atorvastatin. CONCLUSION: These data provide evidence that chronic experimental hypercholesterolaemia produces bone mineralisation in the aortic valve, which is inhibited by atorvastatin.

Animals↗

Spontaneous calcific coronary embolisation: necropsy x-ray study.

Thirty-one hearts with advanced calcification of one or both left heart valves were investigated for the presence of spontaneous calcific emboli. X-ray (Mammograf) showed coronary emboli in 14 cases, that is, in 45% of the whole series. In seven cases (23%) calcific particles were also present in the left ventricular cavity. A total of 265 calcific emboli (205 intracoronary plus 60 intravenous) was demonstrated. The embolisation occurred most frequently and most extensively in association with postrheumatic mitral valve disease. Coronary calcific embolisation must be considered in the differential diagnosis of symptoms of ischaemic heart disease in patients suffering from valvular heart lesions.

Adult↗

A prospective study of patients with CT detected pallidal calcifications.

In a prospective study pallidal calcification was detected in 30 of 1478 (2%) adult patients, on CT brain scans. In 8 cases (26%), the calcifications were detected either years after, or during the course of, conditions known to cause basal ganglia calcification, including AIDS in four cases. Eight patients (three with AIDS) had disturbances of calcium and phosphorus metabolism. It was concluded that: a) pallidal calcification is not uncommon and aetiological factors may be recognised more often than previously reported; b) AIDS is emerging as a significant cause of pallidal calcification in young adults, and c) in AIDS and other conditions, abnormal calcium and phosphate metabolism may act in conjunction with local vascular changes.

Adult↗

Vessel wall calcifications at multi-detector row CT angiography in patients with peripheral arterial disease: effect on clinical utility and clinical predictors.

PURPOSE: To evaluate retrospectively the effect of vessel wall calcifications on the clinical utility of multi-detector row computed tomographic (CT) angiography performed in patients with peripheral arterial disease and to identify clinical predictors for the presence of vessel wall calcifications. MATERIALS AND METHODS: The study was approved by the hospital institutional review board, and informed consent was obtained from all patients. For this study the authors included patients from two randomized controlled trials that measured the costs and effects of diagnostic imaging in patients with peripheral arterial disease. All patients underwent CT angiography and were followed up for 6 months. Clinical utility was measured on the basis of therapeutic confidence (rated on a 10-point scale) in the results of initial CT angiography and the need for additional vascular imaging. Univariable and multivariable logistic and linear regression analysis and the area under the receiver operating characteristic curve were used to evaluate the effect of vessel wall calcifications on the clinical utility of CT angiography and the use of patient characteristics to predict the number of calcified segments at CT angiography. RESULTS: A total of 145 patients were included (mean age, 64 years; 70% men). The authors found that the number of calcified segments was a significant predictor of the need for additional imaging (P = .001) and of the confidence scores (P < .001). The number of calcified segments discriminated between patients who required additional imaging after CT angiography and those who did not (area under the receiver operating characteristic curve, 0.66; 95% confidence interval: 0.54, 0.77). Age, diabetes mellitus, and cardiac disease were significant predictors of the number of calcified segments in both the univariable and multivariable analyses (P < .05). CONCLUSION: Vessel wall calcifications decrease the clinical utility of CT angiography in patients with peripheral arterial disease. Diabetes mellitus, cardiac disease, and elderly age (older than 84 years) are independently predictive for the presence of vessel wall calcifications.

Angiography, Digital Subtraction↗

Early costochondral calcification in adolescent hyperthyroidism.

The finding of extensive costochondral calcification in five adolescents, aged 14-16 years, with hyperthyroidism prompted a retrospective study of all young persons with this condition seen in the last 10 years. Thirty-six patients with hyperthyroidism (ages 13-18 years) were evaluated. Of 32 thyrotoxic teenage girls, 21 (66%) showed some degree of calcification, compared with 73 of 600 (12%) in the control group. Only four boys were evaluated, but one had grade 2 (mild) calcification that was not seen in any boy in the control group. Costochondral calcification increases with age and continues throughout life, reflecting the aging process. The much higher incidence of early costochondral calcification in thyrotoxic adolescents than in the general population is a radiographic indication of advanced bone maturation not previously recognized.

Adolescent↗

Intracranial calcification in the infant and neonate: evaluation by sonography and CT.

This study reports the sonographic and computed tomography (CT) findings in seven infants and neonates with intracranial calcifications and a spectrum of underlying disorders, including toxoplasmosis, cytomegalic inclusion disease, transverse/straight sinus thrombosis, and probable anoxia. Neurotropic infectious disease usually produced clumped or subependymal calcifications accompanied by sometimes bizarre ventricular configurations and prominent periventricular cystic encephalomalacia. Sonography failed to identify prospectively intracranial calcifications in two of the three patients without infection, although calcifications were visible in retrospect. Overall, CT provided optimum visualization of intracranial calcifications.

Brain Diseases↗

Breast calcifications: mammographic evaluation.

Breast calcifications may be categorized as benign, probably benign, and suggestive of malignancy. The interpretation scheme presented here utilizes a systematic structured approach: identify characteristically benign calcifications, for which no further evaluation is needed; define as suggestive of malignancy those remaining calcifications that present as isolated parenchymal clusters of tiny calcific particles; and (optional) attempt to downgrade some of these suspicious calcifications into the "probably benign" category, so that they can be managed by periodic mammographic follow-up rather than biopsy. The clinical acceptability of this approach will vary with local conditions; success in implementing it will encourage increased use of mammography, and ultimately, improved breast health care.

Adenofibroma↗

Coronary artery calcification: assessment with electron beam CT and histomorphometric correlation.

PURPOSE: To assess the reliability of electron beam computed tomography (CT) in the detection of calcific deposits in coronary arteries. MATERIALS AND METHODS: The authors quantitatively evaluated a total of 4,298 segments of coronary arteries with electron beam CT and histomorphometry. RESULTS: Regression analysis of the electron beam CT calcium score versus histomorphometric calcium area produced an r2 value of .92 (r = .96; P < .0001). Ninety-three percent (78 of 84) of all coronary arteries with stenosis of 76%-100% contained calcific deposits, and 20% (17 of 83) of all coronary arteries with stenosis of 0%-50% contained calcific deposits. CONCLUSION: The amount of calcific deposits detected with electron beam CT correlates highly with histomorphometric measurements. Also, the amount of calcific deposits correlates well with the degree of coronary artery stenosis. Electron beam CT, therefore, is a promising noninvasive technique that can help depict the presence and extent of atherosclerotic plaques.

Adult↗

Hyperintense disks on T1-weighted MR images: correlation with calcification.

PURPOSE: To determine if calcification in the intervertebral disk is associated with hyperintensity on T1-weighted spin-echo magnetic resonance (MR) images. MATERIALS AND METHODS: Sagittal T1-weighted MR images that showed one or more hyperintense intervertebral disks and correlative computed tomographic (CT) scans, plain radiographs, or both, were obtained in 11 patients retrospectively and in 43 patients prospectively. Six patients underwent MR imaging with a fat-suppression technique. Histologic analysis of two disks was performed. RESULTS: Absence of calcification was associated with disks that were isointense relative to normal disks (P < .001), mild to moderate calcification was associated with hyperintense disks (P < .001 and P = .004 [two readers]), and both mild to moderate and marked calcifications were associated with hypointense disks (P < .001). Fat suppression resulted in a decrease in hyperintense signal in two patients. CONCLUSION: The results indicate that hyperintensity is associated with calcification. In the absence of clinical findings that suggest other causes, hyperintense disks are suggestive of degenerative disk disease.

Adult↗