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Calcium oxalate microcrystalline-associated arthritis in end-stage renal disease.

Chronic renal failure is known to be associated with secondary hyperoxalemia and the deposition of calcium oxalate in visceral organs, bones, and cartilage. We report the identification of calcium oxalate crystals in the synovial fluid of three patients with chronic renal failure. In one patient, calcium oxalate crystals were also identified within synovium and cartilage. Crystals were pleomorphic and bipyramidal. Some crystals were rod-like and had positive birefringence, thus tending to be confused with calcium pyrophosphate dihydrate when observed with only compensated polarized light microscopy. In one patients asymptomatic effusions were associated with joint capsule calcification, but otherwise normal knee radiographs. The other two patients had bilateral knee pain, one having coexistent features of osteoarthritis and the other chondrocalcinosis. Samples of proliferative synovium, joint capsule, and cartilage from the patient with chondrocalcinosis showed abundant calcium oxalate crystals, and not calcium pyrophosphate dihydrate or calcium hydroxyapatite. Thus, radiographically typical chondrocalcinosis may be due to calcium oxalate. Joint disease in chronic renal failure may be associated with calcium oxalate as well as the previously recognized apatite deposition.

Aged↗

Calcium crystal-associated arthropathy (pseudogout) in a dog.

Calcium pyrophosphate dihydrate (Ca2P2O7.2H2O) crystal-associated arthropathy (pseudogout) was diagnosed in a dog. Clinical signs included non-weightbearing lameness, signs of pain on joint manipulation, and high rectal temperature. Arthrocentesis of carpal joints revealed extra- and intracellular crystals containing calcium. The suspected cause was polyarthritis secondary to chronic Ehrlichia infection. Results of joint tap performed after resolution of the clinical signs were negative for calcium pyrophosphate dihydrate crystals.

Animals↗

The application of atomic force microscopy for the detection of microcrystals in synovial fluid from patients with recurrent synovitis.

Synovial fluid from 33 patients with inflammatory arthritis was examined with a polarized light microscope (PLM) and an atomic force microscope (AFM). Two samples were imaged with a transmission electron microscope (TEM) to determine calcium/phosphate ratios and identify microcrystals of calcium pyrophosphate dihydrate and octacalcium phosphate. Additional correlative x-ray diffraction studies were performed on several samples including purified hydroxyapatite and sodium chloride crystals. Monosodium urate, calcium pyrophosphate dihydrate, hydroxyapatite, octacalcium phosphate, and cholesterol crystals were identified with AFM. AFM images of these microcrystals revealed detailed surface topology, including lattice parameters and structural irregularities at the crystals' surface. These features were consistent with those obtained by TEM and x-ray diffraction studies. In addition, AFM images revealed that some specimens contained microcrystals that were undetected by PLM and/or TEM. These results suggest that AFM may provide a simple yet powerful technique for the detection of microcrystals in synovial fluid taken from patients with crystal-induced arthritis.

Arthritis↗

Classification of primary articular chondrocalcinosis.

Based on long-term observations the authors submit a categorization of primary (hereditary and solitary) articular chondrocalcinosis into three different sub-populations. Attention is drawn to the fact that the extent of the qualitative disorder of the articular cartilage, obviously conditioned genetically, is linked with the age factor and determines the quantitative differences of pyrophosphate arthropathy in primary chondrocalcinosis. In young age, as a rule in the third decade, severe polyarticular condrocalcinosis (first sub-population) develops which causes relatively soon invalidity, in middle age (5th and 6th decade) milder condrocalcinosis develops (second sub-population) which combines with extraarticular, tendinous and tissue calcifacations, and finally in advanced age oligoarticular chondrocalcinosis develops (third sub-population) which is usually associated with ankylosing hyperostosis of the spine. Articular chondrocalcinosis (CCA) which we described by this term as a special metabolic arthropathy which occurs in families and solitary and which we defined as a special nosological unit (35, 36,) has become generally known and firmly established in rheumatology. As ensues from numerous publications, primary (idiopathic) CCA which comprises the hereditary and solitary (sporadic) form is characterized by pyrophosphate arthropathy which develops on articular cartilages not damaged by another process (13, 25, 26, 37); on the other hand as secondary CCA we consider pyrophosphate arthropathies which are associated with metabolic, endocrine or other diseases (9, 30). The common sign of both basic forms of CCA is the presence of microcrystals of calcium pyrophosphate dihydrate (CaPD) in articular cartilages, synovial fluid, or other articular structures (capsules, tendons, ligaments), characterized originally by McCarty et al. (11, 18) and later by other authors (2, 23, 27, 32). In addition to semantic (terminological) problems there were also questions of the classification of CCA because, based on an analysis of major groups of patients, it was revealed that there is a varied picture of chondrocalcinosis or pseudogout (18, 19) or deposition disease (17). of calcium pyrophosphate dihydrate crystals. In our paper we are presenting our view on the primary form of CCA and submitting the characteristics of classification which ensued from more than 20 years observation of our group of patients, in particular based on the evaluation of the beginning of the clinical and X-ray manifestations and the further development of the disease.

Adult↗

The reactivity of neutrophils at the site of an acute inflammatory reaction as measured by chemiluminescence.

In this study the technique of luminol-enhanced chemiluminescence (LECL), which was shown to be dependent on the generation of superoxide anion, has been employed to investigate the reactivity of polymorphonuclear leukocytes found at the site of inflammation. Cells derived from the pleural cavity of rats undergoing an acute inflammatory reaction initiated by an intrapleural injection of calcium pyrophosphate or normal serum demonstrated a significantly higher chemiluminescent response compared to cells derived from animals injected with plasma, saline or phosphate-buffered saline. In addition in vitro studies showed that calcium pyrophosphate crystals could stimulate the cells per se and could increase their reactivity.

Animals↗

Calcium crystals and cartilage damage.

Recent advances in understanding the pathogenesis and mechanisms whereby calcium crystals contribute to cartilage damage are highlighted in this review. Studies that help elucidate pathologic crystal formation in cartilage are discussed. The effect of calcium pyrophosphate dihydrate crystals on the progression of joint degeneration in vivo is noted. Early-onset osteoarthritis and chondrocalcinosis are linked to chromosome 8q. A syndrome of chondrocalcinosis associated with recurrent childhood seizures is linked to chromosome 5p. An unusual destructive and hypertrophic arthropathy of the atlantoaxial joint in calcium pyrophosphate dihydrate crystal deposition disease is described.

Calcium↗

Factors affecting radiographic progression of knee osteoarthritis.

OBJECTIVES: To evaluate the prognostic significance of patient characteristics and radiographic features at the knee for outcome of knee osteoarthritis. METHODS: This was a prospective observational study of 350 osteoarthritic knees. Clinical and radiographic data were obtained on 188 hospital referred patients (mean age 70, range 34-91 years). RESULTS: Median duration of follow up was two years (range 1-5 years). The majority of patients (48%) reported deterioration, but 23% experienced improvement in symptoms during the study period. Reported exercise tolerance remained unchanged in the majority (62%) and deteriorated in 35%. Change in at least one individual radiographic feature of osteoarthritis was seen in 252 (72%) knees: increase in joint space narrowing occurred in 52%, osteophyte in 32%, cysts in 19%, sclerosis in 14%, and attrition in 30%. Increase in Kellgren grade occurred in 137 (39%) knees. Knee effusion, osteoarthritis at multiple joint sites, and nodal change associated with change in Kellgren grade (odds ratios 1.03, 2.39, and 1.80; 95% confidence intervals (CI) 1.01 to 1.05, 1.16 to 4.93, and 1.02 to 3.17, respectively); warmth at the knee associated with change in any radiographic feature (odds ratio 2.22; 95% CI 1.19 to 4.14). Development of, or increase in, attrition and joint space narrowing associated with worsening symptoms and function and occurred with increased frequency in knees with effusions, clinical warmth and calcium pyrophosphate crystals in synovial fluid (p < 0.05). CONCLUSIONS: A high rate of change, radiographic more than clinical, was seen in osteoarthritic knees during this study. Poor clinical and radiographic outcome associated with calcium pyrophosphate crystal deposition and clinical inflammation as reflected by knee effusion and warmth.

Adult↗

Some commonly unrecognized manifestations of metabolic arthropathies.

The metabolic arthropathies are characterized by the deposition of abnormal substances in or around joints. Certain features of some of these arthropathies and their significance have only recently been recognized and others have been insufficiently emphasized. An important group of conditions are the arthropathies related to renal failure and its treatment, namely, aluminum toxicity, periarticular calcification and crystal deposition, hyperparathyroidism, and dialysis-related amyloidosis. Crystal deposition diseases, specifically, gouty arthritis, calcium pyrophosphate deposition, and calcium hydroxyapatite deposition, are also reviewed.

Aluminum↗

Synthesis of hydroxyapatite via mechanochemical treatment.

Hydroxyapatite powder was synthesized with calcium pyrophosphate (Ca2P2O7) and calcium carbonate (CaCO3) through solid-state reaction. The two powders were mixed in acetone and water, respectively, and the single phase of hydroxyapatite was observed to occur only in the powder milled in water, without the additional supply of water vapor during heat-treatment at 1100 degrees C for 1 h. The results were explained in terms of the mechanochemical reaction that could supply enough amount of hydroxyl group to the starting powders to form a single phase of hydroxyapatite. Practical implication of the results is that the powder of high crystalline hydroxyapatite can be obtained by the simple milling in water and subsequent heat-treatment.

Bone Substitutes↗

Comparative calcification of native articular cartilage matrix vesicles and nitroprusside-generated vesicles.

OBJECTIVE: Articular cartilage matrix vesicles generate calcium pyrophosphate- and basic calcium phosphate-like mineral in vitro. We sought to determine the morphologic features and calcifying capacity of sodium nitroprusside (SNP)-induced vesicles for comparison to those of controls. METHODS: Porcine articular cartilage was exposed to 1 mM SNP for 24 h and vesicles were isolated by enzymatic digestion and serial ultracentrifugation. Control vesicles were derived from an equal weight of untreated articular cartilage. Vesicles-containing fractions pelleted at 2 x 10(5) g x min (pellet I), 3 x 10(6) g x min (pellet II, the heavy vesicle fraction) and 8 x 10(6) g x min (pellet III, the light vesicle fraction) were analysed for Lowry protein content, nucleoside triphosphate pyrophosphohydrolase specific activity (NTPPPH) and ATP-dependent calcifying capacity. RESULTS: Electron micrographs (EM) revealed two populations of vesicular structures in both SNP and control pellets. In most experiments, there were no significant differences between the protein contents or ATP-dependent calcium accumulation of SNP vesicles compared to control vesicles. SNP vesicles in pellets I and II had lower NTPPPH activities than their respective controls, P < or = 0.01. CONCLUSIONS: Our data confirmed that 24-hour treatment with the apoptosis-inducing agent did not increase matrix vesicle protein or alter the calcifying activity of vesicles compared to those from control cartilage. SNP did generate vesicles with lower NTPPPH specific activity in most experiments. SNP vesicles, although morphologically similar to controls, are not biochemically identical to them.

Animals↗

Synthesis of nanosized hydroxyapatite powders.

Hydroxyapatite powder was mechanochemically synthesized from calcium pyrophosphate (Ca2P2O7) and calcium carbonate (CaCO3) using a solid-state reaction. The two powders were mixed in distilled water, milled for 8 hours, dried and calcined at 1100 degrees C for 1 hour. The phase(s) formed was analyzed by x-ray diffraction (XRD). It was found that hydroxyapatite was not the only one formed. This result will be used as the starting point to produce a single-phase hydroxyapatite in terms of excess hydroxyl group in a mechanochemical reaction.

Biocompatible Materials↗

Camptodactyly, polyepiphyseal dysplasia and mixed crystal deposition disease.

A sporadic case of camptodactyly and arthropathy is described in a 54-year-old man. Polyepiphyseal dysplasia complicated by the so called "chondrodysplastic rheumatism" was a main feature of the arthropathy which included early onset osteoarthritis, calcium pyrophosphate dihydrate and calcium phosphate deposition diseases. We suggest that epiphyseal dysplasia, chondrocalcinosis and mixed crystal deposition disease could be an additional cause of a camptodactyly-arthropathy syndrome.

Calculi↗

Scanning electron microscopic study of microcrystals implicated in human rheumatic diseases.

Scanning electron microscopy has been used in conjunction with wavelength dispersive X-Ray spectroscopy and in correlation with X-Ray diffraction to define the populations of crystals present in rheumatic diseases. Microcrystals of monosodium urate, triclinic and monoclinic calcium pyrophosphate dihydrate, apatite, calcium hydrogen phosphate dihydrate and corticosteroids, among others, have been found in synovial fluid, in the intraarticular tissues (fibrocartilage, cartilage, and synovial membrane), and in the periarticular tissues (tendons and ectopic calcifications). Scanning electron microscopy in conjunction with wavelength dispersive X-Ray spectroscopy has made it possible to detect microcrystals, even isolated, to describe their morphologies, and to study their relations with the cells of the synovial fluid and with the collagenous and cellular structures of the synovial membrane and of the cartilage. It cannot replace X-Ray diffraction for the conclusive identification of microcrystals, but it can certainly help to improve the analysis of the various populations of crystals present in articular and periarticular rheumatic diseases.

Arthritis, Rheumatoid↗

Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia.

BACKGROUND: Hypophosphatasia (HP) is an inborn error of bone metabolism characterized by a genetic defect in the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP). There is a lack of knowledge as to how the variability and clinical severity of the HP phenotype (especially pain and walking impairment) are related to metabolic disturbances or impairments, subsequent to the molecular defect. METHODS: We analyzed the changes in clinical symptoms and the prostaglandin (PG) metabolism in response to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in six children affected by childhood HP. In addition, by exposing HP fibroblasts to pyridoxal phosphate and/or calcium pyrophosphate in vitro, we analyzed whether the alterations in PG levels are sequelae related to the metabolic defect. RESULTS: Childhood HP patients, who often complain about pain in the lower limbs without evident fractures, have systemic hyperprostaglandinism. Symptomatic anti-inflammatory treatment with NSAIDs significantly improved pain-associated physical impairment. Calcium pyrophosphate, but not pyridoxal phosphate, induced cyclooxygenase-2 (COX-2) gene expression and PG production in HP and normal fibroblasts in vitro. CONCLUSION: Clinical features of childhood HP related to pain in the lower legs may be, at least in part, sequelae related to elevated PG levels, secondary to the primary metabolic defect. Consequently, NSAID treatment does improve the clinical features of childhood HP.

Adolescent↗

Study of biochemical behavior of some exported and nonexported hepatic proteins during an acute inflammatory reaction in the rat.

Haptoglobin, albumin, glucose-6-phosphatase, p-nitrophenol uridine diphosphate (UDP)-glucuronosyltransferase and cytochrome P-450 were measured in liver microsomes from normal rats and from rats undergoing an acute inflammatory reaction (AIR) induced either by subcutaneous administration of turpentine or by intrapleural injection of calcium pyrophosphate. 24 h after the beginning of the AIR induced by subcutaneous administration of turpentine, haptoglobin and albumin, two exported proteins, had risen to a peak (+313%), and dropped considerably (-52%) whereas nonexported protein levels did not change except for cytochrome P-450, which diminished (-38%). In the same way, intrapleural injection of calcium pyrophosphate was followed after 24 h by significant but smaller variations in haptoglobin (+60%) and cytochrome P-450 (-20%) concentrations. Albumin levels, glucose-6-phosphatase and p-nitrophenol UDP-glucuronosyltransferase activities were unchanged in this experimental model. The drop in cytochrome P-450 under all these conditions and also the diminution of albumin in the first model suggest that all the proteins produced by liver cells might not be synthesized in equal amounts. The decrease in cytochrome P-450 could interfere in hepatic drug metabolism during an AIR.

Acute Disease↗

Intra-articular milk of calcium in saturnine gout.

Radiographs of two patients with saturnine gout (lead gout) demonstrated radio-opaque material which resembled milk of calcium within several joints. A histochemical examination of knee aspirate of one of the patients revealed a combination of monosodium urate and calcium pyrophosphate dihydrate. Subsequently, the authors suspected that the findings of intra-articular milk of calcium were due to the coexistence of saturnine gout and calcium pyrophosphate dihydrate deposition disease rather than intra-articular calcified tophus.

Adult↗

Arthritis associated with crystals containing calcium.

Varying combinations of acute inflammatory and/or chronic degenerative arthritis have been found to be associated with crystals of calcium pyrophosphate dihydrate (CPPD) and/or basic calcium phosphates (BCPs). Since the arthropathies associated with CPPDs and/or BCPs occur in older individuals, while diagnosis and treatment for monosodium urate monohydrate crystal deposition disease (gout) have become extremely precise and effective, joint problems associated with calcium crystals have become more common than those associated with monosodium urate monohydrate crystals. The classification, pathogenesis, clinical manifestations, and treatment of CPPD and BCP crystal deposition are discussed.

Aged↗

Detection of crystals in synovial fluids by light microscopy: sensitivity and reliability.

Polarised light microscopy of synovial fluid is an established diagnostic technique widely regarded as reliable for the detection of crystals. The threshold concentration of crystals which can be detected has been investigated and the sensitivity and specificity of six observers compared. Various concentrations of laboratory manufactured crystals of monosodium urate monohydrate (MSUM), calcium pyrophosphate dihydrate (CPPD), and basic calcium phosphates (BCP) were added to the synovial fluid. The threshold for reliable identification of MSUM and CPPD was in the range of 10-100 micrograms/ml. False positives were frequent. The mean sensitivity of the six observers for MSUM was 69% and for CPPD was 82%. The mean specificity for MSUM was 97% and for CPPD was 78%. There was much discrepancy in the results of the slides stained with alizarin red S. Thus the value of alizarin red S as a screening test for BCP is questioned. In view of the variable sensitivity and specificity of different observers for MSUM and CPPD and the concentration threshold for reliable crystal identification, greater caution in the interpretation of synovial fluid analysis is advised, and recommendations for increased quality control are supported.

Anthraquinones↗