Frequent Calcification Research Articles

Effects of bisphosphonate and calcium carbonate on normal aortic valve and cholecalciferol induced in vivo rabbit aortic stenosis model

Abstract Background Calcific aortic valve disease (CAVD) is the most common valvular heart disease. Bisphosphonates are stable analogs of pyrophosphates and commonly prescribed in the treatment of osteoporosis. The effects of bisphosphonate treatment on CAVD are not clearly known and there are inconsistent results. Similarly, the effect of calcium supplementation on CAVD remains controversial. Purpose The aim of this study was to assess the effects of bisphosphonate therapy on the normal aortic valve and vitamin D induced in vivo rabbit aortic stenosis (AS) model. Methods The impact of calcium supplementation on the rabbit AS model was also evaluated. A total of 30 New Zealand white rabbits were divided into five equal groups: no treatment (Group I); 25,000 IU/day vitamin D3 (cholecalciferol) (Group II, rabbit AS model); 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate (Group III); 20 μg/kg/week intravenous alendronate (Group IV) and 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate plus 20μg/kg/week alendronate (Group V). Echocardiography was performed at baseline and after 12 weeks of treatment. The left ventricular mass index (LVMI), aortic valve area (AVA), transvalvular velocities and gradients were recorded. Radiologic and histopathologic examination was performed at the end of the 12th week. Control animals displayed no abnormalities of the aortic valve. Results There was no echocardiographic change in Group IV. In Groups II, III and V, there was a significant decrease in AVA and increases in transvalvular velocities and gradients. However, these stenotic changes were significantly prominent in Group V (p=0.001 for all, via repeated measures ANOVA). Moreover, LVMI was only increased in Group V (p<0.05). Calcification of aortic valvar complex was detected in 14 (46.7%) cases by radiologic imaging and 10 (33.3%) cases by histopathologic examination. Most frequent calcification was found in Group V (5 for each method, 83.3%). Agatston, volume and equivalent mass scores of calcific foci in Group V were significantly higher than other groups (p<0.05 for all). There was no significant difference between groups regarding with presence of osteoclasts in calcific foci. Conclusion Calcium supplementation has no effect on the in vivo rabbit AS model. Alendronate treatment aggravates the stenosis and increases the calcification in the rabbit AS model. Alendronate treatment has no effect on the normal valve in which there was no osteogenesis and osteoclastogenesis. Based on these findings, in patients with CAVD, alendronate treatment should be given with regular echocardiographic follow-up or may not be preferred. Central figure Funding Acknowledgement Type of funding source: None

Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-\u03b21, hypoxia, and COL1A1/HtrA1 siRNAs

Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages. The chondrogenic lineage of BM-MSCs was induced in collagen scaffolds, under normoxia or hypoxia, by BMP-2 and/or TGF-β1. The best chondrogenic induction, with the least hypertrophic induction, was obtained with the combination of BMP-2 and TGF-β1 under hypoxia. Differentiated BM-MSCs were then transfected with siRNAs targeting two markers overexpressed in OA chondrocytes, type I collagen and/or HtrA1 protease. siRNAs significantly decreased mRNA and protein levels of type I collagen and HtrA1, resulting in a more typical chondrocyte phenotype, but with frequent calcification of the subcutaneously implanted constructs in a nude mouse model. Our 3D culture model with BMP-2/TGF-β1 and COL1A1/HtrA1 siRNAs was not effective in producing a cartilage-like matrix in vivo. Further optimization is needed to stabilize the chondrocyte phenotype of differentiated BM-MSCs. Nevertheless, this study offers the opportunity to develop a combinatory cellular therapy strategy for cartilage tissue engineering.

Diagnosis of neonatal ovarian torsion: Emphasis on prenatal and postnatal sonographic findings.

Our aim was to retrospectively review the imaging findings of patients with neonatal ovarian torsion, emphasizing prenatal and postnatal sonographic findings. Eleven patients who had had neonatal ovarian torsion diagnosed surgically (n = 9) or clinicoradiologically (n = 2) were enrolled. Prenatal and postnatal sonographic features, including sequential postnatal change, were reviewed. Clinical and pathologic features were also investigated. All patients except one had a fetal ovarian cyst (mean, 5.3 cm) detected on third-trimester sonography, either simple (n = 6) or complex (n = 4). In all 11 patients, initial postnatal sonography had revealed a complex cyst (mean, 4.7 cm) with intracystic clot or debris, the double-wall sign, a fluid-fluid level, and multiple septation. None of the patients had had symptoms or signs related to the ovarian torsion. Follow-up sonography in seven patients had revealed increased echogenicity of the cyst wall with frequent calcification and a decrease in size of the cyst. In two patients, the interval of the change in cyst position was noted, and autoamputation of the torsed ovary had been surgically confirmed. Serous cystadenoma had been identified in one patient. Neonatal ovarian torsion most commonly manifests as an asymptomatic complex cyst on sonography due to torsion of a fetal ovarian cyst. Serial monitoring of a fetal ovarian cyst for its resolution or changes in its appearance is mandatory for making an early diagnosis of torsion. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:290-297, 2016.

Characteristics of Rib Cartilage Calcification in Asian Patients

IMPORTANCE Rib cartilage from the sixth, seventh, and eighth ribs offers a long cartilaginous curvature, making the material reliable for grafting. Calcification of cartilage causes unexpected absorption, difficult manipulation, and donor site morbidity. Most studies of calcification were performed in Western countries. OBJECTIVE To investigate the incidence, degree, and pattern of rib cartilage calcification in Asian patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of computed tomographic scans of the chest in 120 patients (60 male and 60 female). The incidence, degree, and pattern of cartilage calcification of the sixth through eighth ribs were noted. The patients were stratified into 6 age groups, and 20 patients (10 male and 10 female) were selected for each group. The degree of calcification was assessed as 0%, 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100%. Meaningful calcification was defined as 26% or greater. The pattern of calcification was classified as marginal, granular, and central. EXPOSURE Computed tomographic scans of the chest. MAIN OUTCOMES AND MEASURES Degree of calcification, presence of meaningful calcification, and calcification pattern. RESULTS Overall, 50.8% of cartilage was calcified, and female patients showed more frequent calcification than male patients (59.4% vs 42.2% [P < .001]). Calcification rates of the sixth and seventh rib cartilage were higher than those of the eighth rib cartilage in all age groups except teenagers, who had a similar rate for all 3 ribs. Calcification of the sixth and seventh rib cartilage significantly increased with age. A meaningful calcification rate was very low in males younger than 60 years, whereas the rate was relatively higher in females than males for all age groups. Males predominantly had the marginal type of calcification, whereas females predominantly had a granular type. The rate and pattern of calcification had no relationship to age. CONCLUSIONS AND RELEVANCE In Asian patients, males younger than 60 years show a very low incidence of calcification, whereas females 30 years or older show a relatively high incidence of meaningful calcification. Asian females also show a predominantly granular or central pattern of calcification that may hinder proper harvest and incision of the rib cartilage. These differences in the incidence and pattern of rib cartilage calcification need appropriate preoperative attention.

Salivary duct carcinomas: clinical and CT and MR imaging features in 20 patients

Salivary duct carcinoma (SDC) is an uncommon high grade adenocarcinoma of the salivary gland with a grave prognosis. The aim of this study was to investigate the clinical and CT and MR imaging features of SDC. We retrospectively evaluated the clinical and CT and MR imaging findings in 20 patients (14 men and six women; mean age, 59years) with histologically proved SDC. We also tried to correlate clinicoradiological tumor staging with pathologic tumor staging in 17 patients who underwent surgery. The tumor originated in the parotid gland (n = 11; 55%), the submandibular gland (n = 7; 35%) and the buccal space along the distal Stensen's duct (n = 2; 10%). Locoregional recurrence occurred in 41% and distant metastasis in 47%. Fifty-eight percent died of the disease with a mean survival period of 32months after diagnosis. On CT and MR images, SDC was mostly seen as an ill-defined (85%) and infiltrative (60%) mass with frequent calcification (50%) and necrosis (80%). Although various signal intensities were seen on MR images, six of nine tumors contained the areas of marked hypointensity on T2-weighted images. Clinicoradiological tumor staging correlated well with pathologic tumor staging in 82% of the patients. Ill-defined, infiltrative mass with calcification on CT scans and the areas of marked hypointensity on T2-weighted MR images may be useful radiologic features to suggest the diagnosis of SDC. CT and MR imaging are useful for staging of SDC.

From the archives of the AFIP. Cerebral intraventricular neoplasms: radiologic-pathologic correlation.

Intraventricular neoplasms are readily seen on cross-sectional images, but the myriad possibilities may make a focused differential diagnosis elusive. Consideration of the tissue within and composing the ventricular lining and the clinical findings provide the means to limit the differential diagnosis when analyzing an intraventricular mass on an imaging study. Ependymomas are typically calcified, are more common in children, are more common in the fourth ventricle, and show intense enhancement on contrast-enhanced images. Subependymomas and central neurocytomas have an affinity for the anterior portion of the lateral ventricle, and both commonly demonstrate a heterogeneous cystic appearance on cross-sectional images. Subependymomas are more common in older adults, whereas central neurocytomas are more common before 40 years of age. Subependymal giant cell astrocytomas always lie near the foramen of Monro and are characterized by frequent calcification, intense enhancement on contrast-enhanced studies, and the presence of other stigmata seen in tuberous sclerosis. When a mass is centered on the choroid plexus, a highly vascular tumor-either choroid plexus papilloma, choroid plexus carcinoma, meningioma, or metastasis-should be suspected. The characteristic heavily lobulated appearance of a choroid plexus tumor favors this diagnosis over other possibilities, although it is not always possible to distinguish between the more common benign form, the choroid plexus papilloma, and the less common malignant counterpart, the choroid plexus carcinoma. By using clinical, demographic, and imaging findings, one can significantly limit the differential diagnosis for many of the most common intraventricular neoplasms.

Childhood meningioma: unusual location, atypical radiological findings, and favorable treatment outcome.

To investigate the characteristics of childhood meningioma, especially, locations, radiological findings, pathological features (including proliferative potential) and outcome, 11 children with meningiomas were retrospectively analyzed. Unusual location, large size, frequent calcification, and cyst formation were characteristic radiological findings. Gross total resection was achieved in 8 patients, and there was recurrence in 2. Gamma knife radiosurgery was performed on residual and recurrent tumors. MIB-1 indices tended to be high in large tumors. Nine patients had a Karnofsky Performance Scale of more than 70 during the follow-up period of 10 months to 19.5 years. Surgical treatment rendered 4 of 5 epileptic patients seizure free. The childhood meningiomas examined had unusual locations, atypical radiological findings, and various proliferative potentials. Complete resection is the treatment of choice. Gamma knife radiosurgery can be a good alternative for residual tumors and small recurrent tumors. The outcome of childhood meningiomas is good after surgery.

Fatal sporadic medullary carcinoma of the thyroid.

Thirteen cases of fatal sporadic medullary carcinoma of the thyroid (MCT) that killed the patient within 1 year after diagnosis were compared with 12 nonfatal MCTs with excellent prognosis. Males predominated in fatal cases whereas the reverse was true in MCTs with good prognosis. The two groups of tumors showed generally similar cytoarchitectural features. Outstanding features of fatal MCTs, as compared with nonfatal ones, included more cellular atypia, less frequent amyloid stroma and calcification, higher mitotic rate, tumor necrosis, and a generally lower proportion of neoplastic cells stained for calcitonin. We believe that the morphological features based on routine histological studies, together with immunohistochemistry, should be reported by the pathologist since they could be useful for the management and follow-up of patients with MCT.

THROMBOSIS IN THE NEWBORN

Venous thrombosis was present in 45 newborn infants in a series of 4,000 cases reviewed. The incidence in infants of diabetic mothers was 15.8 per cent (13 of 82 cases), compared to an incidence of less than 1 per cent in the remaining cases. The adrenal and renal veins were most frequently involved, each comprising one third of the cases. Thrombosis was associated with hydramnios, toxemia, birth trauma, sepsis, and recent surgery. Infection and surgery were contributing factors in infants of nondiabetic mothers, whereas a history of hydramnios and toxemia occurred more frequently in infants born to diabetic women. The latter survived for shorter periods, and the thrombus in these cases showed more frequent organization and calcification, suggesting intrauterine formation.