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PubMed1975

Joint effusions, chondrocalcinosis and other rheumatic manifestations in hypothyroidism. A clinicopathologic study.

Twelve patients with severe hypothyroidism and rheumatic signs and symptoms were studied before or within four days of receiving thyroid replacement therapy. Eight patients had synovial effusions. Seven effusions were extremely viscous and six contained calcium pyrophosphate crystals. Leukocyte counts were less than 1,000/mm3, except in two patients during crystal-induced synovitis. "Bulge signs" were present but often sluggish, possibly because of the viscosity of the fluid. Flexor tendon sheath thickening, joint laxity and popliteal cysts were documented. All patients complained of generalized stiffness and two had proximal myopathy. Roentgenograms were obtained in 11 patients, and chondrocalcinosis was identified in seven. Needle synovial biopsy specimens in five patients showed only mild inflammation in the thick synovium. These findings can suggest hypothyroidism, a treatable disease, as the cause of musculoskeletal problems.

Aged↗

PubMed1989

[Experimental study on the application of calcium phosphate bioceramics in repairing periodontal osseous defects].

Two kinds of Tricalcium phosphate Ceramic (TPC) powder and one kind of Calcium pyrophosphate Ceramic (CPC) powder, all prepared by the research group, were used in the animal study. The tissue response to these ceramic and biocompatibility of the ceramic were evaluated histopathologically. First, eighteen male mongrel dogs were divided randomly into six groups, and then, both in mandible and maxilla eight 2-wall osseous defects were created bilaterally in each dog. At each side of jaw, one defect remained empty while the other three defects were implanted with TPC and CPC. The dogs were sacrificed at 2, 4, 8, 16, 24 and 32 weeks after implantation for histologic observation.

Animals↗

PubMed1988

Calcium-acidic phospholipid-phosphate complexes in human hydroxyapatite-containing pathologic deposits.

The deposition of calcium-containing crystals in tissues is due to a combination of factors: elevation in the concentrations of precipitating ions, formation of specific nucleators, and removal of macromolecules that inhibit crystal deposition. This study tested the hypothesis that calcium acidic phospholipid phosphate complexes, which promote hydroxyapatite deposition both in vitro and in vivo, are associated only with hydroxyapatite deposits, and furthermore, that the presence of these complexes is associated with all such hydroxyapatite deposits. Lipid analysis of 76 surgical specimens containing evidence of pathologic calcification (35 hydroxyapatite, 35 calcium pyrophosphate dihydrate, and 6 containing other crystalline materials) had mean complexed acidic phospholipid contents of 8.7, 1, and 0.012, (microgram/mg demineralized dry weight) respectively. Tissues that contained larger, more perfect hydroxyapatite crystals based on x-ray diffraction analyses, had a higher complexed acidic phospholipid content (7.5 +/- 4 micrograms/mg demineralized dry weight, N = 16) than tissues with poorly crystallized hydroxyapatite (3.9 +/- 2 micrograms/mg, N = 11). Histologically, tissues containing larger crystals were characterized by cell or tissue necrosis. Poorly crystalline deposits were found in tissues showing little or no evidence of cell necrosis or tissue degeneration.

Calcinosis↗

PubMed1994

Effect of bioactive ceramic composition and structure on in vitro behavior. III. Porous versus dense ceramics.

In vitro reaction kinetics of surface transformations of porous and dense bioactive ceramics were studied after immersion in simulated physiologic solution (SPS). Porous ceramics with identical macroporosity were commercially obtained: calcium carbonate marine coral (I-CC), coralline HA (I-HA), and a product, labeled as beta-tricalcium phosphate, which was partially transformed into beta-calcium pyrophosphate (I-beta-CP). Previously studied dense ceramics were used for comparison: Ca-deficient HA (CDHA), stoichiometric HA, both well and not well crystallized (wc and nwc s-HA), beta- and alpha-tricalcium phosphate (beta- and alpha-TCP). The induction time to precipitation increased as follows: CDHA, nwc HA < wc HA, I-HA < beta-TCP, I-CC << I-beta-CP. The reaction kinetics of ceramics with identical macroporosity varied substantially depending on composition, crystal structure, and ultrastructure. One of the porous ceramics, I-beta-CP, showed an inhibiting effect on precipitation reactions.

Biotransformation↗

PubMed1987

Chondroid bone arises from mesenchymal stem cells in organ culture of mandibular condyles.

Mandibular condyles of fetal mice 19 to 20 days in utero comprising clean cartilage and its perichondrium were cultured for up to 14 days, and their capacity to develop osteoid and to mineralize in vitro was examined. After 3 days in culture the cartilage of the mandibular condyle appeared to have lost its inherent structural characteristics, including its various cell layers: chondroprogenitor, chondroblastic, and hypertrophic cells. At that time interval no chondroblasts could be seen; instead, most of the cartilage consisted of hypertrophic chondrocytes. By that time, the surrounding perichondrium, which contains pluripotential mesenchymal stem cells, revealed the first signs of extracellular matrix enclosing type I collagen, bone alkaline phosphatase, osteonection, fibronectin, and bone sialoprotein as demonstrated by immunofluorescent techniques. Electron microscopic examinations of the newly formed matrix revealed foci of mineralization within and along collagen fibers as is normally observed during bone development. The composition of the latter mineral deposits resembled calcium pyrophosphate crystals. Following 14 days in culture larger portions of the condyle revealed signs of osseous matrix, yet the tissue reacted positively for type II collagen. Hence, the condylar cartilage, a genuine representative of secondary-type cartilage, elaborated in vitro a unique type of bone that would be most appropriately defined as chondroid bone. Biochemical assays indicated that the de novo formation of chondroid bone was correlated with changes in alkaline phosphatase activity and 45Ca incorporation. The findings of the present study imply that mesenchymal stem cells that ordinarily differentiate into cartilage possess the capacity to differentiate into osteogenic cells and form chondroid bone.

Animals↗

PubMed2004

Crystal-induced inflammation of the kidneys: results from human studies, animal models, and tissue-culture studies.

Calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid or urate are the most common crystals seen in the kidneys. Most of the crystals evoke an inflammatory response leading to fibrosis, loss of nephrons, and eventually to chronic renal failure. Of the three, CaOx monohydrate is the most reactive, whereas some forms of CaP do not evoke any discernible response. Reactive oxygen species are produced during the interactions between the crystals and renal cells and are responsible for the various cellular responses. CaOx crystals generally form in the renal tubules. Exposure of renal epithelial cells to CaOx crystals results in the increased synthesis of osteopontin, bikunin, heparan sulfate, monocyte chemoattractant protein 1 (MCP-1), and prostaglandin (PG) E2, which are known to participate in inflammatory processes and in extracellular matrix production. CaOx crystal deposition in rat kidneys also activates the renin-angiotensin system. Both Ox and CaOx crystals selectively activate p38 mitogen-activated protein kinase (MAPK) in exposed tubular cells. CaP crystals can form in the tubular lumen, tubular cells, or tubular basement membrane. Renal epithelial cells exposed to brushite crystals produce MCP-1. Basic CaP and calcium pyrophosphate dihydrate induce mitogenesis in fibroblasts, stimulate production of PGE2, and up-regulate the synthesis of metalloproteinases (MMP) while down-regulating the production of inhibitors of MMPs through activation of p42/44 MAPK. Deposition of urate crystals in the kidneys becomes associated with renal tubular atrophy, interstitial fibrosis, and development of inflammatory infiltrate. Renal epithelial cells exposed to uric acid crystals synthesize MCP-1 as well as PGE2. Monocytes or neutrophils exposed to urate crystals produce tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6, and IL-8. Expression of IL-8 is mediated through extracellular signal-regulated kinase 1 (ERK-1)/ERK-2 and nuclear transcription factors activated protein 1 and nuclear factor kappabeta. Urate crystals also stimulate the macrophages to produce MMPs.

Animals↗

PubMed2000

Expression of cartilage intermediate layer protein/nucleotide pyrophosphohydrolase parallels the production of extracellular inorganic pyrophosphate in response to growth factors and with aging.

OBJECTIVE: To evaluate the role of the extracellular inorganic pyrophosphate (ePPi)-generating ectoenzyme cartilage intermediate layer protein/nucleotide pyrophosphohydrolase (CILP/NTPPH) in chondrocyte PPi elaboration, we studied CILP/NTPPH expression in response to growth factors during aging. METHODS: Porcine chondrocytes from adult (3-4-year-old) and young (2-week-old) animals were stimulated with transforming growth factor beta1 (TGFbeta1), which enhances ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which diminishes ePPi elaboration. Measurements of ePPi, NTPPH enzyme activity, Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR), and Northern blot analysis were performed. RESULTS: Elaboration of ePPi into conditioned media from adult chondrocytes was significantly increased by TGFbeta1 and significantly inhibited by IGF-1, but no significant differences were observed in young chondrocytes. The protein levels of CILP/NTPPH by Western analysis in the media from adult and young porcine chondrocytes were increased by TGFbeta1. RT-PCR and Northern analysis showed that CILP/NTPPH messenger RNA (mRNA) expression in both adult and young chondrocytes was increased by TGFbeta1 and decreased by IGF-1, but these changes were less significant in the young chondrocytes. Basal and TGFbeta1-up-regulated levels of CILP/NTPPH expression were higher in adult chondrocytes than in young chondrocytes. CONCLUSION: These results provide evidence that CILP/NTPPH expression and ePPi elaboration are concomitantly stimulated by TGFbeta1 and down-regulated by IGF-1, especially in adult chondrocytes, implicating CILP/NTPPH as a functional participant in ePPi elaboration. Increased CILP/NTPPH mRNA expression in chondrocytes derived from aged animals compared with young animals might promote the formation of calcium pyrophosphate dihydrate crystals in aged cartilage.

Aging↗

PubMed1999

Holmium:YAG laser lithotripsy: A dominant photothermal ablative mechanism with chemical decomposition of urinary calculi.

BACKGROUND AND OBJECTIVE: Evidence is presented that the fragmentation process of long-pulse Holmium:YAG (Ho:YAG) lithotripsy is governed by photothermal decomposition of the calculi rather than photomechanical or photoacoustical mechanisms as is widely thought. The clinical Ho:YAG laser lithotriptor (2.12 microm, 250 micros) operates in the free-running mode, producing pulse durations much longer than the time required for a sound wave to propagate beyond the optical penetration depth of this wavelength in water. Hence, it is unlikely that shock waves are produced during bubble formation. In addition, the vapor bubble induced by this laser is not spherical. Thus the magnitude of the pressure wave produced at cavitation collapse does not contribute significantly to lithotripsy. STUDY DESIGN/MATERIALS AND METHODS: A fast-flash photography setup was used to capture the dynamics of urinary calculus fragmentation at various delay times following the onset of the Ho:YAG laser pulse. These images were concurrently correlated with pressure measurements obtained with a piezoelectric polyvinylidene-fluoride needle-hydrophone. Stone mass-loss measurements for ablation of urinary calculi (1) in air (dehydrated and hydrated) and in water, and (2) at pre-cooled and at room temperatures were compared. Chemical and composition analyses were performed on the ablation products of several types of Ho:YAG laser irradiated urinary calculi, including calcium oxalate monohydrate (COM), calcium hydrogen phosphate dihydrate (CHPD), magnesium ammonium phosphate hexahydrate (MAPH), cystine, and uric acid calculi. RESULTS: When the optical fiber was placed perpendicularly in contact with the surface of the target, fast-flash photography provided visual evidence that ablation occurred approximately 50 micros after the initiation of the Ho:YAG laser pulse (250-350 micros duration; 375-400 mJ per pulse), long before the collapse of the cavitation bubble. The measured peak acoustical pressure upon cavitation collapse was negligible (< 2 bars), indicating that photomechanical forces were not responsible for the observed fragmentation process. When the fiber was placed in parallel to the calculus surface, the pressure peaks occurring at the collapse of the cavitation were on the order of 20 bars, but no fragmentation occurred. Regardless of fiber orientation, no shock waves were recorded at the beginning of bubble formation. Ablation of COM calculi (a total of 150 J; 0.5 J per pulse at an 8-Hz repetition rate) revealed different Ho:YAG efficiencies for dehydrated calculus, hydrated calculus, and submerged calculus. COM and cystine calculi, pre-cooled at -80 degrees C and then placed in water, yielded lower mass-loss during ablation (20 J, 1.0 J per pulse) compared to the mass-loss of calculi at room temperature. Chemical analyses of the ablated calculi revealed products resulting from thermal decomposition. Calcium carbonate was found in samples composed of COM calculi; calcium pyrophosphate was found in CHPD samples; free sulfur and cysteine were discovered in samples composed of cystine samples; and cyanide was found in samples of uric acid calculi. CONCLUSION: These experimental results provide convincing evidence that long-pulse Ho:YAG laser lithotripsy causes chemical decomposition of urinary calculi as a consequence of a dominant photothermal mechanism.

Holmium↗

PubMed1999

Diagnosis of crystal-induced arthritis by synovial fluid examination for crystals: lessons from an imperfect test.

OBJECTIVE: Diagnosis of the crystal-induced arthritides is primarily based on microscopic identification of crystals in synovial fluid. Therefore, we aimed to estimate the operating characteristics of this test and demonstrate its clinical use. METHODS: Medline was searched for relevant studies. Sensitivity and specificity of identification of crystals were calculated, as were measures of interobserver agreement. Likelihood ratios were calculated and curves constructed using the solutions to the Bayesian equations. RESULTS: Four studies were identified. The rates of interobserver agreement were low; the false-negative rates in identifying calcium pyrophosphate crystals were particularly high. Only one study allowed calculation of the test operating characteristics, and this was a study that used synthetic crystals and therefore may not be directly useful in a clinical setting. CONCLUSION: There is a paucity of data about the accuracy of crystal identification. As it is clearly not a perfectly sensitive and specific test, the most prudent diagnostic strategy, as with essentially all diagnostic tests, is to establish a posterior probability of disease from a prior probability, based on the clinical features of the patient. Determining the operating characteristics of this test in conventional and reference laboratories should be a research priority for high quality clinical research on crystal arthropathies.

Adult↗

PubMed1978

Immunoglobulin in tophi and on the surface of monosodium urate crystals.

By means of immunohistologic techniques IgG, IgM, and to a lesser degree, IgA were found in the intercrystalline matrix of gouty tophi. Smaller amounts of IgG and IgM were inconstantly found in association with tissue deposits of calcium pyrophosphate. When a technique of immune agglutination was used, the affinity of all three major classes of immunoglobulin to the surface of monosodium urate (MSU) crystals was demonstrated. Immunoglobulin and fibrin were found on MSU aspirated from large tophi.

Agglutination↗

PubMed1980

Familial chondrocalcinosis. Prevalence in Northern Spain and clinical features in five pedigrees.

The first-degree consanguineous relatives of 46 patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease were examined for the presence of articular chondrocalcinosis. In 5 cases the process was familial, with 17 persons in the oldest living generation (mean age 69 +/- 7.4) showing radiographic evidence of calcified cartilage. The clinical syndrome was characterized by a female predominance, late onset of symptoms with mild arthritic manifestations, and oligoarticular chondrocalcinosis. These data suggest that the familial type of CPPD crystal deposition disease is more frequent than formerly thought.

Adolescent↗

PubMed1983

Hereditary chondrocalcinosis in a Mexican-American family.

In a study of 45 adults in a family of Mexican-Indian ancestry, it was found that 22 (49%) had joint symptoms resembling those of degenerative joint disease. Eleven family members had radiographic evidence of chondrocalcinosis, and 1 adult and 3 adolescents had clinical histories and examinations consistent with the familial arthropathy, but no radiographic evidence of disease. The cause of the arthritis in the affected family members is calcium pyrophosphate crystal deposition. The mode of inheritance appears to be autosomal dominant with a high degree of penetrance. The disease is characterized by onset in the second to fifth decades of either episodes of acute inflammatory arthritis or degenerative joint disease. A unique finding of this study was a "halo" surrounding chondrocytes in 1 patient's cartilage, demonstrating loss of the proteoglycans.

Adult↗

PubMed1984

Destructive spondylarthropathy in hemodialyzed patients. A new syndrome.

Spinal radiologic lesions suggestive of destructive spondylarthropathy were found in 10 patients on long-term hemodialysis. These lesions were characterized by severe narrowing of the intervertebral disc, associated with erosions and geodes of the adjacent vertebral plates without osteophytosis. In 9 of the 10 patients the lesions were located in the cervical spine, and in 1 patient, in the lumbar spine. Microbial spondylitis, degenerative disc disease, and destructive spondylarthropathy of calcium pyrophosphate dihydrate deposition disease were each, in turn, ruled out. The finding of apatite crystals by transmission electron microscopy in 1 disc specimen suggests that these crystals may be associated with destructive vertebral disc lesions in dialysis patients.

Aged↗

PubMed1984

Cartilage nucleoside triphosphate (NTP) pyrophosphohydrolase. I. Identification as an ecto-enzyme.

When 1 mM ATP was added to ambient media of canine cartilage in organ culture or canine chondrocytes in monolayer culture, PPi was generated linearly over 4 hours. The appearance of PPi was related to an ectoenzyme based upon its ability to act upon extracellular substrate, to generate extracellular products, failure to detect enzyme activity in supernatant media, failure to increase activity by cell disruption, and susceptibility to digestion by extracellular trypsin. The enzyme responsible for PPi generation is nucleoside triphosphate (NTP) pyrophosphohydrolase, which acts upon a number of purine and pyrimidine nucleoside triphosphates. This enzyme may play a role in generation of extracellular PPi which participates in calcium pyrophosphate dihydrate crystal formation.

Adenosine Triphosphate↗

PubMed1987

Variation in synovial fluid analysis by hospital laboratories.

A survey of 42 hospitals revealed that the frequency of synovial fluid analysis was low (mean 3.9 per month). The mean was skewed upward by a higher frequency in 3 teaching hospitals, such that the overall median was 1.5 per month, with 15 hospitals studying 1 or less per month. There did not appear to be any consensus regarding what constitutes a routine synovial fluid analysis. Technical errors occurred, including dilution with acetic acid for cell counts and inappropriate use of automated cell counters. Twenty-six laboratories studied 4 "unknown" fluids for crystals. In 50 opportunities to detect each crystal type, calcium pyrophosphate was detected only 6 times, and sodium urate was detected 39 times. The white blood cell count reported for a single fluid ranged from 2,467-12,000/mm3 (mean +/- SD 6,683 +/- 1,992). The proportion of neutrophils identified varied from 0-30% (mean +/- SD 13.8 +/- 8.6). The majority of respondents believed that training and reference materials related to synovial fluid analysis should be improved.

Diagnostic Tests, Routine↗

PubMed1988

Synovial complications of spondylepiphyseal dysplasia of late onset.

We describe 2 patients with a late-onset type of spondylepiphyseal dysplasia who developed multiple synovial complications. The synovial manifestations in the first patient included recurrent episodes of acute arthritis due to calcium pyrophosphate dihydrate crystal deposition and, later, chronic synovitis with radiologically evident chondrocalcinosis. In the second patient, cholesterol crystals in synovial fluid, multiple osteochondromata, and a histologic appearance resembling pigmented villonodular synovitis on synovial biopsy were seen. Osteochondromata were identified in 4 other members of this patient's family. Synovial manifestations in the osteochondrodysplasias may be more common than previously recognized.

Acute Disease↗

PubMed1988

Serum and plasma inhibit neutrophil stimulation by hydroxyapatite crystals. Evidence that serum alpha 2-HS glycoprotein is a potent and specific crystal-bound inhibitor.

Tissue deposits of basic calcium phosphate (BCP) crystals are associated with various clinical manifestations of inflammation. We addressed the possibility that native proteins modify the ability of hydroxyapatite (HA) crystals to stimulate human inflammatory cells. Neutrophil superoxide release and chemiluminescence in response to HA crystals (0.3-4.0 mg/ml) were blunted by serum and plasma. Inhibitory activity was progressively removed from serum by sequential adsorption with HA crystals, suggesting that the inhibitors were crystal-bound proteins. Thus, we characterized HA crystal-bound plasma proteins by O'Farrell gels: Fibronectin, transferrin, albumin, alpha 2-HS glycoprotein (AHSG), alpha 1-proteinase inhibitor, alpha 1-acid glycoprotein, Gc globulin, haptoglobin, and high density lipoprotein apolipoproteins were major bound species. Of these, AHSG was the most active inhibitor of HA-induced neutrophil superoxide release, and this glycoprotein partially (60%) restored inhibitory activity to HA-adsorbed serum. AHSG also bound in vitro to the related BCP crystal, octacalcium phosphate, but only minimally to calcium pyrophosphate dihydrate crystals and monosodium urate crystals. Suppressive effects on neutrophil stimulation exhibited by AHSG were also specific for BCP crystals. AHSG was present in noninflammatory synovial fluids bound to synthetic HA crystals in vitro, and AHSG could be detected on native synovial fluid HA crystals. We conclude that the binding of AHSG may modulate the inflammatory potential of BCP crystals.

Blood Physiological Phenomena↗

PubMed1994

Familial spondyloepiphyseal dysplasia tarda, brachydactyly, and precocious osteoarthritis associated with an arginine 75-->cysteine mutation in the procollagen type II gene in a kindred of Chiloe Islanders. I. Clinical, radiographic, and pathologic findings.

OBJECTIVE: To characterize a kindred of Chiloe Islanders with spondyloepiphyseal dysplasia tarda (SEDT), brachydactyly, precocious osteoarthritis (OA), and intraarticular calcification. METHODS: Sixteen family members underwent a complete physical examination, anthropometric measurements, radiographic studies of the spine and peripheral joints, and analysis of the type II procollagen gene (COL2A1). RESULTS: Seven family members presented with SEDT, brachydactyly, precocious OA, and periarticular calcification while 2 others had the same syndrome but without brachydactyly. The inheritance was autosomal dominant, and the disease cosegregated with a base substitution in the COL2A1 gene. CONCLUSION: The syndrome o SEDT, precocious OA, and brachydactyly in a kindred of Chiloe Islanders is associated with a point mutation in 1 allele of the COL2A1 gene. The relationship of this type of SEDT to familial calcium pyrophosphate dihydrate deposition disease and idiopathic hip dysplasia, both endemic in Chiloe Islanders, needs to be further investigated.

Adult↗