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Severe calcification of glutaraldehyde-preserved porcine xenografts in children.

Despite the widespread use of glutaraldehyde-preserved porcine xenografts, severe short-term calcification of these valves has been infrequently reported. This report describes four cases of glutaraldehyde-preserved porcine xenografts in the mitral valve position in which severe calcification occurred within 17 to 25 months of implantation. All four patients were children, aged 13 to 15 years. The clinical presentation in all four cases occurred at a late stage when there was severe xenograft obstruction, with acute symptoms of cardiac decompensation in the presence of pulmonary hypertension and right heart failure. There was rapid cardiac deterioration resulting in a low output state and episodic pulmonary edema necessitating urgent mitral valve replacement. In only one case was there clear auscultatory evidence of severe mitral stenosis. Calcification of these xenografts occurred in the presence of normal serum calcium levels and was not related to infective endocarditis. Histologic examination of the calcified xenografts strongly suggested dystrophic calcification resulting from primary collagen degeneration. The exact cause is unclear, but it appears that glutaraldehyde-preserved porcine xenografts may produce severe short-term calcification with acute hemodynamic deterioration necessitating urgent valve replacement and that this accelerated calcification may be a complication in young persons,

Adolescent↗

Aluminum chloride pretreatment of elastin inhibits elastolysis by matrix metalloproteinases and leads to inhibition of elastin-oriented calcification.

Calcification of elastin occurs in many pathological cardiovascular diseases including atherosclerosis. We have previously shown that purified elastin when subdermally implanted in rats undergoes severe calcification and aluminum chloride (AlCl(3)) pretreatment of elastin inhibits calcification. In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl(3) pretreatment. Subdermal implantation of AlCl(3)-pretreated elastin showed significantly lower MMP-9 and MMP-2 activity surrounding the implant as compared to the control implants. AlCl(3) pretreatment also significantly inhibited elastin implant calcification at the seven-day implant period (AlCl(3)-pretreated 4.07 +/- 1.27, control 23.82 +/- 2.24 microg/mg; p<0.0001). Moreover, elastin gel zymography studies showed that gel pretreatment with AlCl(3) inhibited elastolysis by MMP-9. We also demonstrate significant suppression of MMP-2 activity in aortic wall segments of AlCl(3)-pretreated porcine bioprosthetic heart valve implants as compared to control valve implants in sheep mitral valve replacement studies. AlCl(3) pretreatment also significantly inhibited calcification of elastin in this model. Thus, we conclude that aluminum ion binding to elastin prevents MMP-mediated elastolysis and thus prevents elastin calcification.

Aluminum Chloride↗

Heterotopic calcification in abdominal wounds.

BACKGROUND: Heterotopic bone formation in abdominal incisions is a recognized but uncommon sequela of abdominal surgery. The condition of heterotopic bone formation in the abdominal scar may not only cause physical and/or emotional discomfort for the patient but also mimic a retained foreign body or recurrence of a malignant condition. All cases of two surgeons representing a wide variety of general and thoracic surgery were reviewed, and three primary cases and one recurrent case of heterotopic bone formation in an abdominal wound were identified. These cases are compared with the cases available in the English literature to enhance the recognition, appropriate diagnosis, and treatment options available for the patient with this unusual condition. METHODS: All cases for two surgeons representing a variety of general and thoracic surgery were reviewed. Three patients with painful heterotopic calcification of an abdominal incision requiring excision were identified. One patient had undergone an upper midline laparotomy for pancreatitis and the other two had undergone median sternotomy for cardiac surgery. One of these patients developed a painful recurrence of upper linea alba calcification. All patients were male and ranged in age from 51 to 74 years. Primary heterotopic calcification of the upper linea alba occurred between 2 and 4 months for all patients. All cases were treated with excision and primary tissue closure. The case of recurrent calcification occurred 1 1/2 months after primary closure, and was treated with re-excision and 1,200 centirads of postoperative radiotherapy to the incision area over 3 days, starting on postoperative day 1. The 2 cases of primary heterotopic calcification successfully treated with the initial excision have been followed for 2 and 6 years respectively without recurrence. The case of recurrent heterotopic calcification treated with re-excision and postoperative radiotherapy has been followed for 10 months without recurrence.

Abdomen↗

Electron beam tomography for cusp calcification in homograft versus Freestyle xenografts.

BACKGROUND: We have previously shown, by means of electron beam tomography, the pattern of calcification of the aortic root wall of homografts and porcine xenografts after aortic root replacement. However, application of similar methods for cusp calcification raises specific problems that have not been addressed before. METHODS: A new method for localizing and quantifying calcification of the aortic valve cusps has been evolved. Intravenous contrast-enhanced electron beam tomography was introduced to visualize the aortic cusps. This technique was applied to quantify cusp calcification in 37 patients after aortic root replacement with a homograft (group H) or a Medtronic Freestyle valve (group F) at set intervals between 6 months and 2 years. A calcification score in Hounsfield units (HU) and a calcified volume score in cubic millimeters were calculated. RESULTS: The aortic leaflets were clearly visualized in all patients. The mean calcium score in the cusps was 28.8+/-64.4 HU in group F and 62.4+/-66.9 HU in group H (p = not significant). The mean calcified volume score was 327.0+/-425.9 mm3 in group F and 642.0+/-443.0 mm3 in group H (p = not significant). CONCLUSIONS: Contrast enhancement electron beam tomography is a useful tool for quantification of calcium in the aortic valve leaflets. Our preliminary results show a tendency toward more calcification in the homografts. This needs to be studied further in a bigger cohort of patients followed up for longer periods.

Adult↗

Inhibition of bioprosthetic heart valve calcification with aminodiphosphonate covalently bound to residual aldehyde groups.

Calcification is the principal mode of failure of bioprosthetic heart valves (BPHV) fabricated from glutaraldehyde-pretreated porcine aortic valves or bovine pericardium. Covalent binding of aminopropanehydroxy-diphosphonate (APDP) to residual glutaraldehyde in pericardial BPHV tissue was studied as an approach for the inhibition of calcification. BPHV tissue was preincubated in 0.14 M APDP at pH 7.4, 9.0, and 11.0 for various durations (1 hour to 8 days). The need for NaBH4 stabilization of the tissue-bound APDP was also examined in vitro. The bound APDP was determined using 14C-labeled APDP. APDP uptake was dependent on incubation duration and pH. Calcification of APDP-pretreated BPHV was studied using 21-day rat subdermal implants. Calcification inhibition was directly related to the amount of tissue APDP incorporation. Inhibition of calcification to less than 15% of control was achieved with a concentration of bound APDP of greater than or equal to 30 nM/mg dry tissue with more than 1 hour of incubation at pH 11.0 (bound APDP, 33.55 nM/mg; BPHV calcium content = 3.1 +/- 0.9 micrograms/mg). No adverse effects such as rat growth inhibition or disruption of bone architecture were observed after any treatment. Additionally, in vitro, NaBH4 stabilized tissue-bound APDP. In conclusion, APDP covalently bound to residual aldehyde functions markedly inhibited calcification of BPHV tissue. This inhibition was dependent on the amount of APDP incorporated. NaBH4 stabilized APDP-glutaraldehyde covalent bonds.

Aldehydes↗

Expression of matrix Gla protein (MGP) in an in vitro model of vascular calcification.

To investigate the role of matrix Gla protein (MGP), which can bind mineral ions through gamma-carboxylated glutamic acid residues, in vascular calcification, we examined the expression of MGP in an in vitro calcification model by using bovine vascular smooth muscle cells (BVSMC). The expression of MGP mRNA was decreased during BVSMC calcification and its levels were inversely correlated with the quantities of BVSMC calcification. MGP mRNA expression was restored to the level of uncalcified control by inhibiting BVSMC calcification with bisphosphonates. These data suggest that the expression of MGP gene is modulated in the development of vascular calcification.

Alendronate↗

New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study.

The purpose of the present study was to assess the location, severity and progression of radiopaque lumbar aortic calcifications and to evaluate the utility of summary scores of lumbar calcification in a population-based cohort. Lateral lumbar films, obtained in 617 Framingham heart study participants, were analysed for the presence of abdominal aortic wall calcification in the region corresponding to the first through fourth lumbar vertebrae. The severity of the anterior and posterior aortic calcification were graded individually on a 0-3 scale for each lumbar segment and the results were summarized to develop four different composite scores: (1) affected segments score (range 0-4); (2) anterior and posterior affected score (range 0-8); and (3) antero-posterior severity score (range 0-24). The prevalence of aortic calcification was 37% in men and 27% in women at baseline and 86% in both genders at the follow-up exam 25 years later. During the follow-up interval, the mean of the affected segments score increased from 0.7 in men (0.5 in women) to 2.7 (2.8 in women), the mean of the anterior and posterior affected score from 1.2 (0.8 in women) (P = 0.012 for difference between genders) and the mean of the antero-posterior severity score increased from 1.5 (1.3 in women) to 9.3 (10.3 in women). The antero-posterior severity score offered a slight advantage over other composite scores and had the highest inter-rater intra-class correlations. In summary, lumbar aortic calcification can be graded and composite summary scores are reproducible. This technique appears to provide a simple, low cost assessment of subclinical vascular disease.

Aged↗

Neonatal abdominal calcification: is it always meconium peritonitis?

Intraluminal meconium calcifications are a rare cause of neonatal abdominal calcifications and can easily be misinterpreted as meconium peritonitis. We report three patients with anorectal anomalies, rectourethral fistula, and intraluminal calcified meconium. Intestinal stasis and mixing of urine and meconium may be predisposing factors for the calcification of meconium. Intraluminal calcifications appear as discrete punctate flecks within the distribution of the bowel, in contrast to meconium peritonitis, where the calcifications are linear and plaque-like, occurring anywhere in the abdominal cavity and scrotum. Careful differentiation of abdominal calcifications will allow more appropriate planning of the need and timing of surgery and can suggest the possibility of other anomalies that may not be suspected initially.

Abdomen↗

Helical computed tomography angiography is the most efficient test to assess vascular calcifications in the iliac arterial sector in renal transplant candidates.

UNLABELLED: The increased scope of renal transplant indications has lead to a larger number of recipients with vascular problems due to arterial calcifications in the iliac region. Compared to magnetic resonance and conventional arteriography, helical computed tomography angiography (HCTA) accurately depicts arterial diseases, including the location and extent of arterial calcification. The objective of this study was to assess the value of HCTA with maximum-intensity-projection (MIP) reconstruction to evaluate iliac arterial calcifications and stenosis among candidates for renal transplantation. MATERIAL AND METHODS: From December 1997 to March 2002, 114 HCTA scans with MIP reconstruction were performed in candidates for renal transplantation. Included patients fulfilled some of the following conditions: (a) older than 55 years, (b) diabetic, (c) second transplants, and (d) obvious vascular calcifications on plain abdominal x-ray. RESULTS: Among the 114 patients, 33 (29%) were excluded for transplantation due to universal calcification of the iliac arterial sector, and 81 (71%) were included on the waiting list due to the presence of calcium-free areas for the vascular anastomosis. Transplantation, which was attempted in 28 of the 81 patients, was successful in 25 using the area programmed after HCTA analysis. The transplants failed in three cases because no calcium-free area could be found upon surgical examination. CONCLUSION: HCTA with MIP reconstruction makes it possible to draw an exact map of the arterial calcifications of the iliac arterial sector, allowing better recipient selection and accurate planning for the vascular anastomosis and placement of the renal graft.

Angiography↗

Calcification in the renal medulla; a classification based on a prospective study of 2261 necropsies.

Kidneys from 1864 necropsies performed in Brisbane, Australia, and from 397 necropsies performed in Christchurch, New Zealand, were examined macroscopically and microscopically. Three zonal and three focal patterns of renal medullary calcification were defined: (1) Outer medullary cortical calcification seen in hypercalcemic conditions. (2) A band of calcification at the boundary of the inner and outer medullar associated with degenerative changes and correlated with aging and arteriolar disease. (3) Calcification concentrated around the loops of Henle in the papilla, sometimes a striking finding in children and common at all ages. Heavy calcification in this region was injurious to the loops. (4) Fine focal calcification in random distribution throughout the medulla. This lesion was seen in virtually all adult necropsies to some degree. (5) Coarse focal deposits in the papillary region, more common in males and in a hotter climate. (6) Randall's plaques also were common in males and in a hotter climate.

Australia↗

Aortic and mitral valve calcification in patients with end-stage renal disease.

The frequency and aetiology of aortic valve and mitral annular calcification was studied by echocardiography in 87 patients aged 35-70 on maintenance haemodialysis for a mean of 7.5 years (range 0.5-19). Aortic valve calcification (AVC) was found in 24 patients (28%) and mitral annular calcification (MAC) was found in 31 (36%). AVC was severe and produced aortic stenosis in 5 patients with a tricuspid aortic valve (mean age 51.6 years), which confirms that calcific aortic stenosis is a complication of chronic uraemia. MAC was associated with functional mitral stenosis in 1 patient. Premature AVC and MAC were associated with an increased calcium X phosphate product and long-term haemodialysis. There were no significant differences between those patients with aortic stenosis and those with AVC but no stenosis. Patients with AVC had an increased incidence of MAC and vascular calcification. Premature AVC and MAC is frequent in dialysis patients and appears to be related to abnormal calcium and phosphate metabolism and to increased mechanical stress on the valve cusps. In a small but important group of patients on long-term dialysis, premature valve calcification is severe and produces aortic stenosis, or less frequently, mitral stenosis.

Adult↗

Bisphosphonate derivatized polyurethanes resist calcification.

Calcification of polyurethane cardiovascular implants is an important disease process that has the potential to compromise the long-term function of devices such as polymer heart valves and ventricular assist systems. In this study we report the successful formulation and characterization of bisphosphonate-derivatized polyurethanes, hypothesized to resist implant calcification based on the pharmacologic activity of the immobilized bisphosphonate. Fully polymerized polyurethanes (a polyurea-polyurethane and a polycarbonate polyurethane) were modified (post-polymerization) with bromoalkylation of the hard segments followed by attachment of a bisphosphonate group at the bromine site. These bisphosphonate-polyurethanes resisted calcification in rat 60 day subdermal implants compared to nonmodified control polyurethane implants, that calcify. Bisphosphonates-modified polyurethanes were also studied in circulatory implants using a pulmonary valve cusp replacement model in sheep. Polyurethane cusps modified with bisphosphonate did not calcify in 90 day implants. compared to control polyurethane cusps implants, that demonstrated nodular surface oriented calcific deposits. It is concluded that bisphosphonate modified polyurethanes resist calcification both in subdermal implants and in the circulation. This novel biomaterial approach offers great promise for long-term blood stream implantation with calcification resistance.

Animals↗

Sclerosing peritonitis with gross peritoneal calcification: a case report.

We report the case of a patient on dialysis for 13 years, including continuous ambulatory peritoneal dialysis (CAPD) for 11 years, who developed sclerosing peritonitis with gross peritoneal calcification. The patient first presented with abdominal pain in January 1990, when peritoneal calcification was detected for the first time. Her symptoms settled spontaneously and 1 year later she presented with acute peritonitis and adynamic ileus. The peritonitis settled with antibiotics and Tenchkoff catheter removal, but the ileus persisted. She was commenced on long-term parenteral nutrition, but never recovered useful bowel function. After 8 weeks of hemodialysis and total parenteral nutrition, a further laparotomy for an acute abdomen showed what appeared to be extensive bowel infarction and peritoneal calcification. She died several days later. Of significance, peritoneal calcification was first noted on x-ray and computed tomography (CT) scan while the patient was still largely asymptomatic and before peritoneal ultrafiltration capacity was significantly impaired. Unlike other reported cases of calcifying peritonitis, sclerosing peritonitis was present and calcification was far more extensive. It was not associated with factors such as frequent infective peritonitis or acetate dialysate. Calciphylaxis was not present nor was there any abnormality of calcium-phosphate metabolism. The outcome of this case suggests that patients with recurrent or persistent bowel symptoms on long-term CAPD should have early abdominal x-ray or CT scanning to exclude sclerosing peritonitis or bowel calcification. If present, consideration should be given to transferring the patient to another therapeutic dialysis modality if possible.

Adult↗

Impaired tensile strength after shock-wave application in an animal model of tendon calcification.

Extracorporeal shock-wave application facilitates dissolution of rotator cuff calcifications. Therefore, disappearance or disintegration of tendon calcifications by shock waves might be appropriate for any kind of tendon calcification. Here, shock waves with various energy flux densities were applied to the mineralized medial gastrocnemius tendon of turkeys as an animal model. After application of shock waves in vivo, with energy flux density of 0.6 mJ/mm(2), histologic examination and microradiography did not show dissolution or disintegration of tendon calcifications. After shock-wave application in vitro, even for energy flux density of 1.2 mJ/mm(2) neither dissolution nor disintegration of tendon calcifications were observed. Biomechanical testing revealed significant impairment of tensile strength following shock-wave application in vitro, with energy flux density of 1.2 mJ/mm(2), but not with 0.6 mJ/mm(2). These results are important for considerations of clinical extracorporeal shock-wave application on tendon calcifications, as well as on tendon ossifications.

Animals↗

The role of high-resolution ultrasonography in management of calcific tendonitis of the rotator cuff.

This article predicts the possibility of resorption of the calcific plaques in the shoulder using high-resolution ultrasonography (HRUS) and color Doppler ultrasound (CDUS), and evaluates the therapeutic effect of US-guided fine-needle multiple punctures of the calcific plaque. A total of 100 patients with calcific tendenosis were divided into 3 groups: In group 1, patients having chronic shoulder pain received conservative treatment; in group 2, patients having acute exacerbation of shoulder pain also received conservative treatment; and group 3 patients received US-guided fine-needle multiple punctures or aspiration. In CDUS, all images were classified as grade 0 (no color flow signals), grade 1 (weak spotty color flow signal), grade 2 (few rod-like color flow signals), grade 3 (many rod-like or linear color flow signals). In the follow-up study, marked improvement of patients' clinical condition with more than 50% size reduction of calcific plaque was defined as an effective treatment. There was no significant difference between group 1 and group 3 (p = 0.558) in CDUS, but there was a significant difference between group 1 and group 2 (p = 0.000), and group 2 and group 3 (p = 0.000) on the basis of classification of grade < 1 and grade > or = 1. There was also significant difference in the follow-up result of effective management between group 1 and group 3 (p = 0.000), and group 1 and group 2 (p = 0.000). In conclusion, HRUS with CDUS proved to be a good modality in evaluating the possibility of resorption of shoulder calcification and, if CDUS > or = grade 1 in calcific tendonitis, we highly recommend conservative treatment with regular follow-up. On the other hand, if CDUS < grade 1, fine-needle repeated puncture could be considered as an effective alternative treatment.

Adult↗

Phosphate buffer in alkali eye burns as an inducer of experimental corneal calcification.

Corneal calcification is a common problem in severe inflammation, chronic glaucoma, renal disorders and other diseases with disturbed calcium and phosphorus metabolism. The pathogenesis of corneal calcifications in ocular diseases is not yet completely understood. We present a model of an induced corneal calcification by local treatment. In a double-masked experiment 16 rabbits underwent eye burn of one cornea followed by immediate rinsing (160 ml) with isotonic phosphate buffer (n=8) or saline solution (n=8) three time a day for 16 days. Tissues were excised, shock frozen and cut into 10 microm slices, freeze dried and coated with evaporated carbon. In the phosphate buffer group an early onset of corneal opacification occurred resulting in completely white corneas after 16 days, combined with corneoscleral ulceration. The other group showed similar corneal erosion and a little corneal ulceration, but no opacifications. The opacifications of the phosphate buffer group could be identified as calcifications by direct measurements of calcium and phosphate (by energy dispersive X-ray analysis on corneal samples). In conclusion, inappropriate application of phosphate leads to uncontrolled calcifications of the cornea after severe burns to the eye. This reflects clinically observed calcifications after eye burns and possibly the adverse side effects of phosphate buffered eye drops being applied in ophthalmology.

Alkalies↗

Prevalence and patterns of tendon calcification in patients with chondrocalcinosis of the knee: radiologic study of 156 patients.

The presence or absence of tendon calcification was studied at six anatomic sites: Achilles, gastrocnemius, quadriceps, triceps (elbow), triceps long head (shoulder), and rotator cuff. The morphology of the calcifications was categorized in 156 patients with chondrocalcinosis in the knee. Achilles tendon, gastrocnemius, and quadriceps tendon calcifications were most common, ranging from 21%-25% of our patient population was thin linear bands. Triceps calcification at the elbow, rotator cuff calcifications, and long head of triceps tendon calcification were less common.

Adult↗

Computed tomography study of pineal calcification in schizophrenia.

Computed tomography studies concerning pineal calcification (PC) in schizophrenia have been conducted mainly by one author who correlated this calcification with several aspects of the illness. On the basis of these findings the aim of the present study was to analyze size and incidence of pineal gland calcification by CT in schizophrenics and healthy controls, and to verify the relationship between pineal calcification and age, and the possible correlation with psychopathologic variables. Pineal calcification was measured on CT scans of 87 schizophrenics and 46 controls divided into seven age subgroups of five years each. No significant differences in PC incidence and mean size between patients and controls were observed as far as the entire group was considered. PC size correlated with age both in schizophrenics and controls. We found a higher incidence of PC in schizophrenics in the age subgroup of 21-25 years, and a negative correlation with positive symptoms of schizophrenia in the overall group. These findings could suggest a premature calcific process in schizophrenics and a probable association with 'non-paranoid' aspects of the illness. Nevertheless the potential role of this process possibly related to some aspects of the altered neurodevelopment in schizophrenia is still unclear.

Adult↗