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PubMed1989

Tumoral calcium pyrophosphate deposition disease.

A report of two patients in which a soft tissue mass, initially regarded as a malignant tumor, was shown to be the result of calcium pyrophosphate deposition disease. The first case, a woman aged 71 years, presented with a mass involving the right fifth finger. In the second case, also a woman aged 71 years, the lesion involved the tissues adjacent to the right hip. Each lesion consisted of a mass of highly cellular tissue containing deposits of calcium pyrophosphate dihydrate crystals. The clinical, radiological, and pathological features of the two cases are compared with those of seven similar cases reported in the literature.

Aged↗

PubMed1982

Evaluation of renal ischemia with 99mTc-pyrophosphate.

Renal ischemia injury was induced by transient 30-min occlusion of the main artery in five rabbits and by transient 60-min occlusion in four rabbits. The vessels to the contralateral kidneys were ligated in all nine animals and in six additional control rabbits. Renal blood flow was restored immediately following the transient ischemia. Twenty-four hours later, 99mTc-pyrophosphate was injected and renal uptake was monitored for 100 s and 10-min intervals for 90 min following injection. At 90 min postinjection, the animals were killed and the percent injected dose remaining in the kidneys was calculated for three animals in each group. At 60 min postinjection, in vivo activity in the 30-min ischemic kidneys was 2.3 times greater than that of controls, and activity in the 60-min ischemic kidneys 4.6 times greater than that of controls. These results suggest that 99mTc-pyrophosphate scanning may be useful in assessing slight ischemic damage to the kidney.

Animals↗

PubMed1987

Interaction of polymorphonuclear leukocytes with calcium pyrophosphate dihydrate crystals deposited in chondrocalcinosis cartilage.

Electron microscopy was used to investigate the characteristics of calcium pyrophosphate dihydrate (CPPD) crystals in chondrocalcinosis (pseudogout syndrome). Crystals in midzone cartilage were frequently seen adjacent to chondrocytes. Great variation in crystal size and shape was observed. Most of the pyrophosphate crystals that had been phagocytosed by polymorphonuclear leukocytes of synovial fluid from patients with acute pseudogout were small (less than or equal to 1 micron), indicating that small crystals can cause intense inflammation. Large numbers of polymorphonuclear leukocytes became attached to the eroded articular surface and phagocytosed microcrystals. Interaction of polymorphonuclear leukocytes with CPPD crystals in the superficial region of articular cartilage may stimulate the release of inflammatory mediators.

Aged↗

PubMedDate not supplied

Differential diagnosis between secondary hyperparathyroidism and aluminum intoxication in uremic patients: usefulness of 99mTc-pyrophosphate bone scintigraphy.

Forty-one patients in chronic end-stage renal failure and 4 patients with a functioning kidney transplant presented with spontaneous hypercalcemia or intolerance to vitamin D3 sterols and/or oral calcium supplements. Bone iliac crest biopsy with aluminum staining and Tc-pyrophosphate bone scintigraphy with determination of Fogelman score were performed in all cases. Two patients had aluminum-induced osteomalacia (AL O). Thirty-eight biopsies showed renal osteodystrophy (secondary hyperparathyroidism or various combinations of osteitis fibrosa and osteomalacia): 19 with positive staining for aluminum (RO + AL) and 19 without aluminum deposits (RO). The series also comprised 2 cases of pure osteomalacia (OM), 2 cases of osteoporosis (OP), and 1 case of osteoporosis with aluminum accumulation (OP + AL). Mean Fogelman score in RO patients (9.1 +/- 0.3) was significantly higher than in all other categories (5.9 +/- 0.5 for RO + AL, and scores ranging from 0 to 8 in the last 7 patients, p less than 0.01). Patients with massive aluminum accumulation in bone (greater than 75% of the total trabecular surface) showed no or very low uptake of the isotope by the skeleton. Fogelman scores of 9 or higher were always associated with histological secondary hyperparathyroidism. 99mTc-pyrophosphate bone scintigraphy is helpful to distinguish aluminum intoxication from secondary hyperparathyroidism in uremic patients.

Adult↗

PubMed1987

A comparative study of myocardial infarct detection using Tc99m pyrophosphate and In111 DTPA antimyosin (R11D10 Fab).

A crossover study to examine the potential of In111 antimyosin Fab fragment to detect fresh myocardial infarcts in comparison with Tc99m pyrophosphate is reported. In 27 cases indium antimyosin correctly diagnosed 19 patients with infarcts and 4 true negatives. There were also 2 false positive and 2 false negative scintigrams. Tc99m pyrophosphate detected 21 infarcts and 6 true negatives correctly.

Diphosphates↗

PubMed1984

The deposition of calcium pyrophosphate and phosphate by matrix vesicles isolated from fetal bovine epiphyseal cartilage.

Since calcium (Ca) deposition by isolated fetal bovine matrix vesicles is selectively supported by nucleoside triphosphate, and since the Ca deposits appear to be amorphous by transmission electron microscopy, attempts were made to study further the nature of these Ca deposits. Calcification of isolated matrix vesicles was allowed to occur in a calcifying medium in which either inorganic phosphate (Pi) or [gamma-P]ATP was labeled with 32P. 32P in Ca P (pyrophosphate) deposits were analyzed by a Dowex 1 X 10 anion exchange chromatography. The results of the analysis indicate that the (32P) radioactivity was mainly associated with Pi when Pi in the calcifying media was labeled with 32P. In contrast, 32P was found to be associated with inorganic pyrophosphate (PPi) when [gamma-32P]ATP was used. Using a specific enzyme coupling assay for PPi, the presence of PPi in the Ca deposits was demonstrated. The amounts of Pi and PPi in the Ca deposits initiated by fetal calf matrix vesicles were found to be approximately equal. To exclude the possibility that the major part of PPi of Ca P deposit existed as adsorbed form, the deposition was performed under the conditions in which Pi was omitted from calcifying medium. The results of these experiments showed that substantial amount of PPi and Ca deposits remained the same and was not correlated to the amount of Pi in these deposits. In contrast, Pi of CaP was decreased if Pi was omitted from the calcifying medium. Thus, it appears that the major portion of PPi exists as mineral rather than adsorbed form.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1996

Retinoic acid stimulates pyrophosphate elaboration by cartilage and chondrocytes.

Abnormal metabolism of extracellular inorganic pyrophosphate (PPi) by articular cartilage contributes to calcium pyrophosphate dihydrate (CPPD) crystal formation and the resultant arthritis known as CPPD deposition disease. The factors causing excess PPi elaboration in affected cartilage remain poorly defined. Retinoic acid (RA), a naturally occurring vitamin A metabolite, promotes cartilage degeneration and mineralization, two correlates of CPPD crystal deposition. RA was examined as a potential modifier of cartilage PPi elaboration. All-trans RA (200-1000 nM) increased PPi levels in culture medium of normal porcine cartilage and chondrocytes 2-3-fold over control values at 96 hours of incubation (P < 0.01). IGF1 and anti-EGF antibody diminished the effects of RA on PPi elaboration. RA modestly increased activity of the PPi-generating ectoenzyme NTPPPH in culture medium (P < 0.01). As some RA effects are mediated through increased activity of TGFbeta, a known PPi stimulant, we examined the effect of anti-TGFbeta antibody on RA-induced PPi elaboration. PPi levels in medium were reduced from 30 +/- 7 microM in cartilage cultures with 500 nM RA to 14 +/- 4 microM PPi in cartilage cultures with RA and anti-TGFbeta. Anti-TGFbeta antibody, however, had no significant effect on RA-induced PPi elaboration in chondrocyte cultures. Thus, RA, along with TGFbeta and ascorbate, can now be included in the list of known PPi stimulants. All three of these factors promote mineralization in growth plate cartilage. These data support a central role for TGFbeta in CPPD disease, and provide further evidence linking processes of normal and pathologic calcification in cartilage.

Animals↗

PubMed2002

Idiopathic widespread calcium pyrophosphate dihydrate crystal deposition disease in a young patient.

We report a case of generalized chondrocalcinosis in a 34-year-old man with no familial or medical history of associated diseases. Radiographs revealed calcification of the articular cartilages of the limbs, the fibrous rings around the intervertebral disks, the triangular cartilages of the wrists, and the pubic symphysis. On the basis of the presence of calcium pyrophosphate in the synovial fluid of his right ankle and generalized chondrocalcinosis, the patient was diagnosed with idiopathic calcium pyrophosphate dihydrate (CPPD) crystal deposition disease. Nonsteroidal anti-inflammatory drugs and steroid treatment provided symptomatic relief.

Adult↗

PubMed2004

[Calcium pyrophosphate dihydrate-crystal induced arthropathy].

Calcium pyrophosphate dihydrate (CPPD) crystal induced arthropathy (CPPD-CA; systemic articular chondrocalcinosis) characterized by deposition of CPPD-crystals in fibro- and hyaline cartilage, joint capsule and periarticular tissues is associated with a variable clinical spectrum of inflammatory degenerative and occasionally destructive joint and vertebral manifestations including neurologic complications and rarely tophaceous-tumoral tissue calcifications. Microcrystal formation in the extracellular matrix of cartilage and tendons is based on genetic and acquired dysregulation of chondrocyte pyrophosphate metabolism and presumably linked to gene mutants on the short arm of chromosome-5 (gene locus 5p15.1 and ANKH gene). Idiopathic disease occurs rarely in hereditary-familial and frequently in sporadic manifestation with increasing prevalence due to aging; a secondary form is significantly related to endocrine and metabolic disorders (as to hyperparathyroidism, hemochromatosis etc.). The impact of the clinical syndrome in practice is important in differential diagnosis of age related conditions like acute mono- or oligoarthritis, systemic osteoarthritis and polymyalgia rheumatica. Actual treatment ignores established prevention of systemic cartilage calcification and is oriented to symptomatic relief.

Arthrography↗

PubMed1999

Degeneration of the scaphoid-trapezium joint: a useful finding to differentiate calcium pyrophosphate deposition disease from osteoarthritis.

This study aimed to determine whether osteoarthritis of the scaphoid-trapezium joint (ST osteoarthritis) is associated with calcium pyrophosphate deposition disease (CPDD) in an elderly population with or without concomitant polyarthritis of the finger joints (FIPO). An age- and gender matched case-control study was performed at a university hospital outpatient clinic. Cases and controls were identified from a clinical registry. The case ascertainment process included: (1) chart review for evidence of pyrophosphate crystals from arthrocentesis and/or cartilage calcifications and (2) blinded reading of hand X-rays by three observers for calcification of the triangular fibrocartilage and/or cartilage calcification around the spatium triangulare. Osteoarthritis was graded from 0 to 4 according to the Standard Atlas of Radiographs. The association of ST osteoarthritis with the diagnosis was examined using chi2 tests or the Wilcoxon rank sum test as appropriate. From 65 potential cases, 30 fulfilled the inclusion/exclusion criteria whereas from 185 potential controls, 81 fulfilled the inclusion/exclusion criteria. Thirty controls were matched to cases for gender and age. ST osteoarthritis was much more severe in CPDD (median: 3.0) than in patients with FIPO (median: 0.3) and was strongly associated with the diagnosis (odds ratio 13.8; CI 3.4-59.8). Definite ST osteoarthritis identified CPDD with a sensitivity of 83% and a specificity of 73% with regard to FIPO. It was concluded that the presence of ST osteoarthritis is a helpful diagnostic finding for the diagnosis of CPDD in an elderly, predominantly female population with a high prevalence of FIPO. Especially in cases without radiographic cartilage or fibrocartilage calcification of the wrist, ST osteoarthritis may point to the correct diagnosis.

Aged↗

PubMed1999

Familial and clinical aspects of calcium pyrophosphate deposition disease.

The mechanisms involved in calcium pyrophosphate dehydrated deposition disease (CPPDD) are unknown and those families with the disease, described in different countries, provide a fertile file for genomic research. Genomic DNA studies in these kindred with secondary or primary form of CPPDD provide a shortcut for trying to investigate the biomolecular basis of the disease. Mutations in the COL2A1 gene have been identified in one family with spondyloepiphyseal dysplasia and secondary deposits of pyrophosphate and apatite crystalline deposits. In another kindred with CPPDD due to precocious osteoarthritis, the phenotype was linked to markers of chromosome 8p. In four other kindreds (British, Argentinean, French, and the United States), the phenotypes were linked to a precise region of chromosome 5p. Two possible genes located in this region that are expressed in the articular cartilage, but of unknown articular physiologic role are being investigated as possible CPPDD genes. From the clinical point of view, CPPDD spectrum of clinical and radiographic manifestations is enlarging, especially those related to spine involvement or pseudo tumoral forms. At the end, the present review of a current therapeutic approach for CPPDD is discussed.

Acute Disease↗

PubMed1982

Value of positive myocardial technetium-99m-pyrophosphate scintigraphy in the noninvasive diagnosis of cardiac amyloidosis.

Ten consecutive patients with tissue-proven amyloidosis, seven of whom presented with congestive heart failure, were found to exhibit intense diffuse uptake of technetium-99m-pyrophosphate (Tc-99m-PYP) on cardiac radionuclide imaging. The patients exhibited echocardiographic and systolic time interval abnormalities suggesting combined restrictive and congestive cardiomyopathic changes. On M-mode echocardiograms, there was symmetrically increased thickness of the interventricular septum and left ventricular (LV) posterior wall in diastole (10 of 10), decreased fractional shortening of the LV minor axis diameter in systole (eight of nine), and decreased percent thickening of the LV minor axis diameter in systole (eight of nine) and LV posterior wall (10 of 10) in systole. Three patients demonstrated enlarged LV end-diastolic diameter. All 10 patients had abnormal PEP/LVET and eight had shortened LVETI. When combined with noninvasive tests of LV performance, positive myocardial pyrophosphate (PYP) scanning provides a new and useful adjunct in the diagnosis of amyloid heart disease.

Aged↗

PubMed1987

Early identification of amyloid heart disease by technetium-99m-pyrophosphate scintigraphy: a study with familial amyloid polyneuropathy.

To determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scanning or two-dimensional echocardiography can detect amyloid heart disease in an earlier stage of familial amyloid polyneuropathy, 15 patients were examined. Although 10 of the 15 patients had no clinical evidence of congestive heart failure, as well as normal ventricular wall thickness and normal values for left ventricular systolic function, five (50%) of them showed mild or moderate myocardial uptake. On the other hand, none had characteristic highly refractile myocardial echoes on the two-dimensional echocardiographic images (p less than 0.01), and values for diastolic function were reduced in four of the five and normal in the remaining one. In 85 control subjects, diffuse positive pyrophosphate scans of the heart were found in four (5%) of them (three with dilated cardiomyopathy and one with sarcoidosis), and highly refractile granular sparkling echoes were observed in nine (11%) (five with hypertrophic cardiomyopathy, three with aortic stenosis, and one with hypereosinophilic syndrome). We conclude that Tc-99m-PYP scanning is a more sensitive and specific method and may have the potential ability to detect amyloid heart disease in the earlier stage of familial amyloid polyneuropathy than two-dimensional echocardiography.

Adult↗

PubMed1983

Validation of technetium-99m stannous pyrophosphate myocardial scintigraphy for diagnosing acute myocardial infarction more than 48 hours old when serum creatine kinase-MB has returned to normal.

Determination of lactic dehydrogenase (LDH) isoenzymes is the current method of choice for diagnosing acute myocardial infarction (AMI) greater than 48 hours old. However, other causes of enzyme elevation make the availability of an alternate method of diagnosis worthwhile. Accordingly, serial technetium-99m pyrophosphate scintigrams were obtained in 61 patients with transmural AMI and in 46 patients with subendocardial AMI. Imaging was performed in all 107 patients at the time creatine kinase isoenzyme (CK-MB) was present 37 +/- 18 hours (range 12 to 72) after the onset of AMI, and at the time CK-MB was absent 106 +/- 34 hours (range 48 to 168) after the onset of AMI. At the time CK-MB was absent, the sensitivity using either a regional or a diffuse positive scintigram was 95% (58 of 61 patients) for transmural AMI and 65% (30 of 46 patients) for subendocardial AMI. The sensitivity using a regional positive scintigram was 82% (50 of 61 patients) for transmural AMI and 37% (17 of 46 patients) for subendocardial AMI. The sensitivity using a high-grade regional positive scintigram was 36% (22 of 61 patients) for transmural AMI and 11% (5 of 46 patients) for subendocardial AMI. The specificity was 70% (143 of 204 patients) for either a regional or a diffuse abnormality, 92% (187 of 204 patients) for a regional abnormality, and 100% (204 of 204 patients) for a high-grade regional abnormality. Thus, pyrophosphate scintigraphy is useful in confirming the diagnosis of AMI, particularly transmural, greater than 48 hours old and when CK-MB has returned to normal. A positive scintigram with a high-grade regional abnormality is specific for a recent AMI and may be contributory in establishing the diagnoses when LDH isoenzymes are inconclusive.

Adult↗

PubMed1984

Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: analysis of 357 patients.

One hundred nine patients with persistently positive technetium-99m pyrophosphate (Tc-99m-PPi) myocardial scintigrams 6 months after acute myocardial infarction (MI) (Group A) and 185 patients without such persistently positive scintigrams (Group B) were compared with regard to enzymatically determined infarct size, early and late measurements of left ventricular (LV) function determined by radionuclide ventriculography, and preceding clinical course during the 6 months after MI. The CK-MB-determined infarct size index in Group A (17.4 +/- 10.6 g-Eq/m2) did not differ significantly from that in Group B (16.0 +/- 14.6 g-Eq/m2). Similarly, myocardial infarct areas in the 2 groups, determined by planimetry of acute Tc-99m-PPi scintigrams in those patients with well-localized 3+ or 4+ anterior pyrophosphate uptake, were not significantly different (35.7 +/- 13.4 vs 34.4 +/- 13.1 cm2, respectively). However, patients in Group A had significantly lower LV ejection fractions than those in Group B, both within 18 hours of the onset of MI (0.42 +/- 0.14 vs 0.49 +/- 0.14, p less than 0.01) and at 3 months after MI, both at rest (0.42 +/- 0.14 vs 0.51 +/- 0.14, p less than 0.01) and at maximal symptom-limited supine bicycle exercise (0.44 +/- 0.17 vs 0.51 +/- 0.17, p less than 0.01). Peak exercise levels achieved in the 2 groups were not significantly different. Furthermore, patients in Group A demonstrated a greater incidence of congestive heart failure during the initial hospital admission (41 vs 24%; p less than 0.01) and a greater requirement for digoxin (p less than 0.05) and furosemide (p less than 0.01) after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗

PubMed1989

Myocardial infarction determined by technetium-99m pyrophosphate single-photon tomography complicating elective coronary artery bypass grafting for angina pectoris.

The incidence of acute myocardial infarction (AMI) complicating coronary artery bypass grafting (CABG) has previously been based on concordance of electrocardiographic, enzymatic and scintigraphic criteria. Technetium-99m pyrophosphate (Tc-PPi) single-photon emission computed tomography now enables detection of AMI with high sensitivity and specificity. Using this technique, perioperative AMI was detected in 12 of 58 patients (21%) undergoing successful elective CABG for stable angina pectoris. Stepwise multivariate logistic regression analysis was performed to compare the predictive value of preoperative (New York Heart Association class, left ventricular ejection fraction and use of beta blockers) and intraoperative (number of grafts constructed, use of internal mammary anastomoses, use of sequential saphenous vein grafts, smallest grafted distal vessel lumen caliber and aortic cross-clamp time) variables. Preoperative New York Association class (p = 0.04) and smallest grafted distal vessel lumen caliber (p = 0.03) were significant multivariate predictors of perioperative AMI. Only 1 perioperative patient with AMI (and 1 pyrophosphate-negative patient) developed new Q waves. Serum creatine kinase-MB was higher in patients with AMI by repeated measures analysis of variance (p = 0.0003). Five AMIs occurred in myocardial segments revascularized using sequential saphenous vein grafts, and 7 in segments perfused by significantly stenosed epicardial vessels with distal lumen diameter and perfusion territory considered too small to warrant CABG. At 6-month follow-up, the mean left ventricular ejection fraction increased from 0.61 to 0.65 in Tc-PPI-negative patients (p = 0.01), but not in perioperative patients with AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Monosodium urate and calcium pyrophosphate crystals differentially activate the excitation-response coupling sequence of human neutrophils.

The activation patterns of human neutrophils elicited by unopsonized monosodium urate and calcium pyrophosphate dihydrate crystals were investigated. The parameters chosen, the mobilization of calcium and the synthesis of leukotrienes, are generally accepted to be relevant to the activation of the cells and their pathophysiological roles. Both particles were found to elicit increases in cytoplasmic free calcium and leukotriene synthesis. However, the rank order of potency of these two stimuli was found to be sharply dependent on the test chosen. Monosodium urate crystals were significantly more effective than calcium pyrophosphate dihydrate crystals in terms of calcium mobilization, while the latter are more potent at inducing leukotriene synthesis. These results demonstrate that these two phagocytic particles which are related to separate inflammatory joint diseases differentially activate the excitation-response coupling sequence of human neutrophils.

Arachidonate 5-Lipoxygenase↗

PubMed1988

99mTc-SN-pyrophosphate scintigraphy following traumatic posterior dislocation of the hip.

Avascular necrosis of the head of the femur is a serious complication of traumatic dislocation of the hip joint; therefore 99mTc-SN-pyrophosphate scintigraphy was carried out 10 to 14 weeks (average 12 weeks) after the injury on 12 patients to determine whether it was possible to demonstrate reduced or no activity of the head of the femur before development of radiological avascular necrosis of the head of the femur. Increased activity was observed in 9 of 11 hips with fracture-dislocation of the head of the femur, acetabulum or both, and normal activity was demonstrated in the contralateral hip of all patients. During the follow-up period avascular necrosis of the head of the femur developed in four hips from 6 to 20 months after the accident. It is concluded that 99mTc-SN-pyrophosphate scintigraphy 12 weeks after traumatic dislocation of the hip was unable to identify hips at risk of later development of avascular necrosis of the head of the femur.

Adolescent↗