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Ultrastructural and cytochemical studies on the matrix vesicle calcification in the teeth of the killifish, Oryzias latipes.

Tooth germs of killifish were examined by both ultrastructural and cytochemical methods. The ultrastructure of the dentin in the early calcification stage of its development resembled that of mammals. Numerous extracellular membrane-bounded vesicles, matrix vesicles, were seen in the predentinal space, especially abundantly in the basal portion of the tooth germ. They were more numerous and more uniform in appearance than in any other higher vertebrates. Where calcification was going to start, slightly identifiable needles of apatite crystals were found in the vesicular structures. Crystals increase in number filling up the vesicles and then ther surroundings, finally to form many calcified spherules. Where calcification was more extensive, the matrix vesicles were no longer visible having been buried calcified among spherules. Contrary, to popular belief, there was no relationship seen between collagen fibrils and the initial deposits of minerals, that is, collagen fibrils did not seem to work as the initial site of calcification. Instead, matrix vesicles and plasma membranes of odontoblasts likely were involved in calcification as they both showed alkaline phosphatase activity. The ultrastructural and cytochemical findings from this study thus indicated that calcification of the killifish tooth germs was initiated not in the enamel, but in their dentin by the matrix vesicles which were liberated into the dentin matrix from odontoblasts mainly by way of fragmentation of cell processes.

Animals↗

Criteria for management of calcific metamorphosis: review with a case report.

Calcific metamorphosis is seen commonly in the dental pulp after traumatic tooth injuries and is characterized by deposition of hard tissue within the root canal space. Opinion differs among practitioners as to whether to treat these cases upon early detection of calcific metamorphosis or to observe them until symptoms or radiographic signs of pulpal necrosis are detected. In this article, the clinical, radiographic, and histopathologic appearance of calcific metamorphosis is described; a review of the literature is presented to address these issues in an attempt to establish sound rationale for treatment. Approximately 3.8% to 24% of traumatized teeth develop varying degrees of calcific metamorphosis. Studies indicate that of these, approximately 1% to 16% will develop pulpal necrosis. Most of the literature does not support endodontic intervention unless periradicular pathoses is detected or the involved tooth becomes syptomatic. It may be advisable to manage cases demonstrating calcific metamorphosis through observation and periodic examination. A report of a case where in non-surgical endodontic intervention was successfully carried out a patient suffering from calcific metamorphosis with periapical pathoses is also presented.

Adult↗

[Subungual calcification in the normal nail bed of the toes].

Subungual calcifications in the normal nail bed begin in women during the 3rd decade and obtain an incidence of 47% from the 8th decade. These calcifications appear in men two decades later and obtain in old age an incidence of only 14%. The 1st toe is involved three times as often as the 5th toe. In about 10% the subungual calcifications of the toes are combined with the same subungual calcifications of the digits. Subungual calcifications of the normal nail bed are considered as a normal reaction of ageing, which is not influenced by diseases with a tendency of tissue calcification.

Adult↗

Calcific phacolysis. Salvageable vision following treatment.

Calcific phacolysis has been previously described histopathologically in the enucleated eyes of three patients with unilateral posttraumatic total blindness. Each eye showed dissolution of a mature cataractous lens with dispersion of calcific lens material throughout the globe. We studied a patient in whom the signs of calcific phacolysis developed 19 months following intraoperative dislocation of a cataract into the vitreous. Partial removal of calcific particles was achieved by subtotal vitrectomy and lensectomy, with subsequent penetrating keratoplasty. Corneal histopathological findings showed a deposition of calcified lens particles between Descemet's membrane and retrocorneal fibrous membrane. Despite diffuse retinal calcification, the patient's visual acuity was 20/400. To our knowledge, this is the first report of calcific phacolysis occurring after surgical dislocation of a cataract into the vitreous and wherein treatment resulted in some preservation of vision. Early diagnosis and aggressive therapy may improve the visual prognosis in this condition.

Aged↗

Dystrophic and psammomatous calcifications in a desmoid tumor. A light microscopic and ultrastructural study.

A desmoid tumor occurring in the abdominal wall of a 6-year-old boy with extensive microcalcifications was documented. Two forms of calcifications were observed: an irregular, amorphous dystrophic calcification of the collagen fibers and an organized, laminated psammomatous calcification (psammoma bodies). Ultrastructural studies revealed that the dystrophic calcification is a result of direct mineralization of individual collagen fibrils with subsequent coalescence to form large, calcified masses. Psammomatous calcification tended to cluster around areas where the collagen fibers assumed a whorled configuration. It is suggested that the circular orientation of the collagen fibers in some way favors the laminar deposition of hydroxyapitite crystals. The cause of the pathologic calcifications is the presence of extensive amorphous eosinophilic degeneration of the collagen fibers.

Calcinosis↗

Diamine extension of glutaraldehyde crosslinks mitigates bioprosthetic aortic wall calcification in the sheep model.

We previously have been able to show that fixation at increasing concentrations of glutaraldehyde (GA) leads to mitigated rather than facilitated tissue calcification. The purpose of the present study was to introduce additional crosslinks and provide evidence that crosslink density may be an underlying inhibitory principle. Entire aortic roots were chosen to verify the concept on the challenging aortic wall tissue. Porcine aortic roots were crosslinked with 0.2% GA, 3%GA, and 3% GA containing an interim step that introduced diamine bridges. Crosslink efficiency was determined on the basis of shrinkage temperature (SrT degrees ), resistance to protease digestion (RPD), residual amine analysis (RA), and tensile modulus (E(10)). Calcium levels, calcification patterns, and inflammation were assessed after 6 and 24 weeks of implantation in a sheep circulatory model. Crosslink efficiency in aortic wall tissue was moderately affected by increasing the fixative concentration from 0.2% GA to 3% GA (SrT degrees from 85.7 degrees +/- 0.3 degrees to 87.5 degrees +/- 0.3 degrees C, p < 0.002; RPD from 24.2 +/- 1.2 to 29.1 +/- 0.7%, p < 0.003; RA from 0.069 +/- 0.004 to 0.058 +/- 0.003 micromol/mg, p < 0.03, and E(10) from 1.9 +/- 0.11 to 2.94 +/- 0.34 MPa, p < 0.01), but it was distinctly enhanced when diamine bridges were introduced (SrT degrees from 87.5 degrees +/- 0.3 degrees to 93.4 degrees +/- 0.3 degrees C, p << 0.0001; RPD from 29.1 +/- 0.7 to 68.4 +/- 1.8%, p << 0.0001; and E(10) from 2.94 +/- 0.34 to 6.80 +/- 0.61 MPa, p < 0.0003). Aortic wall calcification was reduced significantly by increasing the GA concentration from 0.2 to 3% [37.8%, p = 0.076 (6 weeks) and 34.0%, p = 0.008 (24 weeks)] and further reduced by the introduction of additional diamine [84.0%, p = 0.006 (6 weeks) and 29.8%, p = 0.037 (24 weeks)]. The combined effect of increased GA concentration plus an interim diamine step on aortic wall tissue resulted in a 90% and 53.7% reduction of calcification after 6 weeks and 24 weeks, respectively. The correlation coefficients between calcification and SrT degrees, RDP, and E(10) was -0.9767, -0.9460, and -0.9740, respectively (6 weeks). The inflammatory host reaction regularly found in 0.2% fixed tissue was practically abolished through the introduction of diamine bridges. Our study demonstrated a distinct correlation between the mitigation of aortic wall calcification and three parameters used to assess crosslink density.

Animals↗

Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy?

BACKGROUND: Calcific aortic stenosis may have common etiological factors with atherosclerosis. HYPOTHESIS: In this retrospective, case-control study, we aimed to determine whether there is an association between hypercholesterolemia and calcific aortic valve stenosis. METHODS: Consecutive patients undergoing single aortic or mitral valve replacement in a regional cardiothoracic surgical center were reviewed and preoperative patient characteristics were recorded: demographics, comorbidity (including coronary artery disease and associated risk factors), serum total cholesterol, lipid-lowering therapy, and serum creatinine. RESULTS: Serum total cholesterol concentrations were significantly higher in patients with calcific aortic stenosis than in controls (6.2+/-1.1 vs. 5.3+/-1.1 mmol/l; p < 0.001). The significant difference in serum cholesterol concentrations remained following correction for gender and body mass index (p = 0.02) and when patients with coronary artery disease were excluded (6.3+/-1.1 vs. 5.3+/-1.4 mmol/l; p<0.001). Subgroup analysis demonstrated that the association between elevated serum cholesterol concentrations and calcific aortic stenosis was particularly strong in patients with tricuspid aortic valves (6.4+/-1.2 vs. 5.3+/-1.1 mmol/l; p < 0.001) compared with those with bicuspid valves (5.9+/-1.1 vs. 5.3+/-1.1 mmol/l; p = 0.06). CONCLUSIONS: We conclude that hypercholesterolemia is associated with calcific aortic stenosis and may be implicated in its pathogenesis and progression. We believe that there is now a need for a randomized, controlled trial of cholesterol-lowering therapy in patients with calcific aortic stenosis.

Aged↗

Thyroid calcification and its association with thyroid carcinoma.

AIM: Calcification within the thyroid gland may occur in both benign and malignant thyroid disease, and its detection on ultrasonography is frequently dismissed by many clinicians as an incidental finding of little significance. As a tertiary referral center, most of our thyroid patients will have had thyroid ultrasonography before being referred to us, and in our experience, the incidence of malignancy in a thyroid nodule containing calcification seems to be higher than that in the average thyroid nodule. To assess this risk, we conducted this retrospective review. MATERIALS AND METHODS: Our analysis included 462 consecutive patients who underwent thyroid surgery at our institution between 1995 and 1999. We reviewed all the patients' charts for data regarding clinical findings, preoperative diagnostic investigations, and histopathologic diagnosis. Of the 462 patients, 361 (78.1%) had thyroid ultrasonography before surgery, and 49 (13.6%) of these ultrasounds showed intrathyroidal calcification. RESULTS: Of the 49 patients whose ultrasounds showed intrathyroidal calcification, 29 (59.2%) were found on histopathologic examination to have thyroid carcinoma. Twelve of the remaining 20 patients had multinodular goiters. Of the 29 patients with malignancy, seven (24.1%) had preoperative fine-needle aspirates that were reported as benign. After excluding patients who were initially seen with multinodular disease, in the subset of 37 patients who presented with a solitary thyroid lesion with calcification, 28 (75.7%) were found to have carcinoma. CONCLUSIONS: When calcification is noted within a solitary thyroid nodule, the risk of malignancy is very high. Surgery should be recommended regardless of the result of fine-needle aspiration cytologic findings.

Calcinosis↗

Coracoclavicular and coracoacromial ligament calcification and ossification.

Thirty-six patients with calcification or ossification at or around the coracoclavicular and coracoacromial regions were analyzed with regard to type, location, and configuration of the deposits and related clinical history. Calcification or ossification in the coracoclavicular region resulted largely from trauma (36%) or renal failure (28%). Trauma patients may develop punctate calcification or ossification but do not develop the tumoral type of calcification. About 5% of the renal failure patients had coracoclavicular ligament calcifications, one-half of which were of the tumoral type. Renal failure patients may have punctate or tumoral calcifications but do not develop ossification.

Adult↗

[Clinical, endocrinological, and computerized tomography scans for symmetrical calcification of the basal ganglia (author's transl)].

Symmetrical calcification of the basal ganglia was found in 2% of 8000 computerized tomography (CT) scans. Of 19 cases, only 2 were detectable on conventional skull films. The less prominent calcifications were most often found in the region of the pallidum, the knee of the internal capsule. Also, the lesions were generally symmetrical. Thus these factors must be considered basic morphological characteristics of the pathophysiological process. Additional neurological disorders were present in 6 patients. Neurological symptoms in the remaining 13, when present, depended on the extent of the lesion. The most common finding was tremor, although disturbances of fine motor control, transient lateralizing signs, and seizures were also noted. No particular constellation of symptoms or signs permitted accurate clinical localization of the lesions. The patients could be divided into three groups on the basis of clinical findings: (1) young people with marked cerebral calcinosis ('idiopathic' calcification of basal ganglia), (2) patients with hypoparathyroidism, and (3) older patients with relatively little calcification. Most patients with calcific lesions will be included in the third group. Any calcification of basal ganglia detected by CT scans demands careful evaluation of calcium metabolism.

Adult↗

Extensive arterial calcification of unknown etiology in a 29-year-old male.

A 29-year-old male with generalized arterial calcification is presented. The roentgenogram showed extensive calcification bilaterally in the facial, brachial, renal, external iliac, femoral, and popliteal arteries. There was also calcification around the joints of the fingers, toes, elbows, and shoulders. The uniformity of arterial calcification in the radiograph differentiated this lesion from Mönckeberg's arteriosclerosis. The serum concentration levels of calcium, phosphorus, alkaline phosphatase, and calcium regulatory hormones were normal. The patient did not have diabetes mellitus, renal disease, or connective tissue disease, thus the etiology of the calcification was not identified. However, a bone scintigram showed that the uptake of 99 mTc-methylene diphosphate was significantly increased in the calcified arteries. Therefore, increased metabolic activity was associated with the derangement leading to arterial calcification.

Adult↗

Patterns of calcifications and cholangiographic findings in hepatobiliary tuberculosis.

The radiologic findings on conventional examinations (plain films and cholangiograms) in a large group of patients with proven hepatobiliary tuberculosis are reviewed. The plain film findings of large "chalky" and confluent hepatic calcifications or nodal-type calcifications along the course of the common bile duct are suggestive of hepatobiliary tuberculosis. Small, discrete, scattered calcifications may be mimicked by histoplasmosis but can be differentiated from hepatobiliary tuberculosis. Obstructing defects seen on cholangiography are indicative of tuberculosis when adjacent calcifications are present. The patterns of liver calcifications could provide a clue to the diagnosis of hepatobiliary tuberculosis and its differentiation from liver calcifications of various other etiologies.

Adolescent↗

Foetal hepatic calcification.

Thirty-three cases of 1,500 spontaneously-aborted foetuses showed hepatic calcifications. The exact location of these calcifications were confirmed by contrast studies, anatomic dissection, and further histology when necessary. Of them, 18 were calcified hepatic vein thrombi (CHVT), 12 were calcified portal vein thrombi (CPVT), 2 were parenchymal calcifications, and one was mixed. Associated anomalies were high (85% of cases). No significant difference was found between the type and percentage of anomalies of those with CHVT and those with CPVT. The most common anomalies encountered in all cases were meconium intraluminal calcification (27%), cystic hygroma (18%), and metaphyseal defect (18%). In view of this, it is suggested that a variety of severe foetal illnesses predispose to CHVT and CPVT. At correlation with maternal factors, it was found that the highest incidence was in the third decade. A significant high percentage of mothers (33%) had been on contraceptive pills, and there was interesting inverse relationship of hepatic calcification with gravidity. Practically, it is also hoped that the awareness of the presence of various types of hepatic calcifications will help in their detection prenatally by ultrasound.

Abortion, Spontaneous↗

Furosemide-related renal calcifications in the premature infant. A longitudinal ultrasonographic study.

Low birthweight infants treated with chronic furosemide therapy are at risk for the development of intrarenal calcifications. A prospective longitudinal renal ultrasound investigation was conducted to study the correlation of diuretic therapy, clinical course and ultrasonographic findings. Of 117 premature infants studied ultrasonographically upon discharge from the hospital, 20 had intrarenal calcifications. Eight patients at age 16.3 +/- 2.6 months had sonographic resolution of renal calcifications, 6.6 +/- 1.1 months after furosemide therapy had been discontinued. Of the 12 patients with persistent calcifications, 4 died from severe pulmonary disease and autopsy in 3 of them confirmed the ultrasonographic diagnosis. All 12 children but 2 continued to receive furosemide for their chronic lung disease demonstrating significant association between chronic use of loop diuretics and persistence fo the renal calcifications (p less than 0.001). Two patients required nephrolithotomy and 4 suffered from recurrent urinary tract infections. In 4 patients, 5 kidneys were of small size and in 2 bilateral collecting system dilation was noted. We conclude that discontinuation of furosemide therapy is associated with resolution of the renal calcifications. On the other hand, continued treatment with furosemide is associated with high renal morbidity which indicates ongoing clinical and ultrasonographic follow-up.

Child, Preschool↗

Ductal adenocarcinoma of the pancreas associated with intratumoral calcification.

An invasive ductal carcinoma of the pancreas with intratumoral calcification is reported in a 59-yr-old female. The calcification was preoperatively demonstrated by ultrasonography and computed tomography. On the cut surface of the resected specimen of the pancreas tail, calcification was observed in the central part of the ductal adenocarcinoma. Although calcification is not uncommon in chronic pancreatitis or serous cystadenoma, mucinous cystadenoma/adenocarcinoma, solid and cystic tumor, and islet cell tumor, intratumoral calcification is uncommon in an ordinary ductal adenocarcinoma of the pancreas. For differential diagnosis from other conditions associated with calcification, careful examinations are necessary.

Calcinosis↗

Idiopathic arterial calcification in childhood.

Idiopathic arterial calcification in infancy is usually fatal with death in early life and diagnosis at post mortem. This report describes a unique, late presentation with hypertension and cardiac failure in a child aged 33 months, found to have widespread arterial calcification at radiological imaging. The calcium-phosphate axis was normal and there was no other demonstrable cause for calcification. Additionally, the histological features of arterial calcification at renal biopsy paralleled the findings in infants with this disorder. The late presentation in this case is unusual and has not been previously reported. Ultrasound and CT are sensitive for calcification, and the disease should be suspected in children presenting with cardiac or respiratory manifestations and features of arterial calcification, where no metabolic cause is established.

Arterial Occlusive Diseases↗

Calcification in calcium pyrophosphate dihydrate (CPPD) crystalline deposits in the knee: anatomic, radiographic, MR imaging, and histologic study in cadavers.

OBJECTIVE: To demonstrate and determine the frequency and location of calcification within cadaveric knees with or without calcification typical of calcium pyrophosphate dihydrate (CPPD), utilizing histologic, radiographic and MR imaging techniques. DESIGN AND PATIENTS: Ten cadaveric knees of elderly individuals that demonstrated no radiographic evidence of prior surgery or trauma were studied with MR imaging and subsequently sectioned in planes corresponding to those obtained with MR imaging. The slices were imaged with high-resolution radiography. Two musculoskeletal radiologists correlated the anatomic, MR and radiographic findings. Three of the knees, which did not demonstrate calcifications, were utilized as controls. Histologic sections were obtained from four knees that contained calcifications and from the three controls, and analyzed with special histologic stains that demonstrate phosphorus and calcium. RESULTS: Radiographic imaging and histologic analysis demonstrated widespread CPPD crystal deposition in four of the 10 knee specimens (40%). MR imaging demonstrated some calcifications only within the articular cartilage of the femoral condyles in three of the four (75%) specimens that had CPPD deposits. In all four specimens radiographs and histologic analysis were more sensitive than MR imaging. Histologic analysis demonstrated no evidence of CPPD crystals in the control specimens. CONCLUSION: MR imaging is insensitive to the presence of CPPD deposits in the knee, even when such deposits are widespread. Our study suggests that the sensitivity of MR imaging was significantly better in detecting CPPD deposits in the hyaline cartilage of the femoral condyles when compared with other internal structures, even when such structures contained a higher amount of calcification.

Aged↗

Detection of coronary artery calcifications predicting coronary heart disease: comparison of fluoroscopy and spiral CT.

The aim of this study was to evaluate the clinical relevance of coronary artery calcifications detected by spiral CT, congruence with fluoroscopy (FS) and coronary angiography, and comparison with studies reporting on application of double-helical CT and ultrafast CT. Forty patients underwent spiral CT (2-mm slice thickness, table feed 3 mm/s), coronary angiography, and FS (performed in the usual manner). Stenosis and calcifications were evaluated semiquantitatively. Nineteen patients suffering from a stenosis >/= 75 % were verified at coronary angiography. All had coronary artery calcification on spiral CT. Fluoroscopy did not detect 8 of 19 patients with a stenosis >/= 75 % (1 vessel: n = 1; 2 vessels: n = 3; 3 vessels: n = 4). In spiral CT sensitivity was 100 % and specificity was 33 % (FS: 58 and 48 %). Positive predictive value was 83 % for spiral CT (FS: 50 %), and negative predictive value was 100 % (FS: 56 %). A significant linear increase in the calcification score was found for increasing maximal stenosis (p < 0.005). Spiral CT is more sensitive than FS in the recognition of hemodynamic relevant stenoses using the detection of coronary artery calcifications. Statistical parameters are comparable to ultrafast-CT. Spiral CT is a suitable non-invasive diagnostic technique in coronary heart disease. Coronary calcifications found incidentally in symptomatic patients at chest CT should be reported to the referring physician for further cardiological workup.

Adult↗