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[Incidence of chondrocalcinosis in a series of 1,000 surgically excised intervertebral disks].

This study is based on the histological examination of a series of 1000 intervertebral discs which were excised surgically for a painful spinal or nerve root syndrome. The authors observed in 31 cases (18 men and 13 women) a chondrocalcinosis that was not found clinically (small circumscribed deposits of crystals identified as calcium pyrophosphate after examination in compensated polarized light microscopy). The frequency is higher than that of chondrocalcinosis observed in the menisci excised surgically from the knees of subjects with the same average age; but it is lower than that for the menisci taken from autopsy material of subjects with a higher average age. The histological examination of all surgically excised discs would permit the findings of signs of chondrocalcinosis, thus emphasizing the risk for the patient of a further evolution to arthropathies (spinal or peripheral). This can offer bases for statistical longitudinal studies.

Adolescent↗

Osteophytosis of the knee: anatomic, radiologic, and pathologic investigation.

Although the radiologic manifestations of degenerative disease of the knee have been investigated, the distribution of marginal and central osteophytes has not been defined. This study included (a) 50 consecutive patients with osteoarthritis of the knee in whom routine and specialized projections were obtained prospectively, (b) 25 patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease whose knee radiographs were retrospectively reviewed, and (c) four cadaveric knees that were dissected to assess pertinent anatomy. In this study the importance of the tunnel view in the evaluation of osteoarthritis and CPPD crystal deposition disease is demonstrated, the distribution of and the relationship between marginal and central osteophytes are discussed, and two new radiologic signs are described. As both marginal and central osteophytes may simulate intraarticular bodies, the recognition of these outgrowths is of clinical importance.

Calcium Pyrophosphate↗

Supravital staining of cells in noninflammatory synovial fluids: analysis of the effect of crystals on cell populations.

Leukocyte differential counts are rarely performed on synovial fluids (SF) with low leukocyte (WBC) counts as they have been difficult to do with standard Wright stains. We performed SF analysis including supravital (SV) stains for differential counts on 100 consecutive relatively noninflammatory synovial fluids defined as any SF with less than 2,000 cells/mm3. SV stains gave clear cellular morphology. Monocytes were the most prominent cells in all noninflammatory synovial fluids. Thirty-eight fluids were found to have crystals (monosodium urate (MSU) in 15, calcium pyrophosphate dihydrate (CPPD) in 5, CPPD plus apatite-like crystals in 9, apatite-like clumps alone in 8 and lipid liquid in 1). WBC counts, percentages of polymorphonuclear (PMN) and absolute PMN counts were greatest in fluids with MSU or CPPD crystals. Fluids with apatite-like clumps alone tended to have the lowest WBC counts. The presence of WBC over 500 cells/mm3, over 20% PMN and absolute PMN counts over 250 cells/mm3 should encourage a careful search for crystals, especially MSU, in noninflammatory synovial fluids.

Apatites↗

Prostaglandin (PG) E2 generation by cultured canine synovial fibroblasts exposed to microcrystals containing calcium.

Immunoreactive prostaglandin (PG) E2 was released into the ambient medium in a dose dependent fashion when either hydroxyapatite (HA) or calcium pyrophosphate dihydrate (CPPD) crystals were added to canine synovial fibroblasts in tissue culture. PGE2 release peaked 6 to 9 hours after HA or CPPD crystals were added in the presence of serum but at 24 hours if they were added in the presence of lactalbumin hydrolysate. PGE2 release correlated with crystal endocytosis estimated qualitatively by serial phase contrast microscopy and time lapse photography. As postulated previously by others for monosodium urate crystals, prostaglandin production by synovial cells may also be related to the pathogenesis of the destructive arthropathies associated with HA or CPPD crystals.

Animals↗

Reproducibility of synovial fluid examination for crystals.

A quality assurance survey of synovial fluid examination for crystals was performed at six teaching hospitals. Aliquots of 12 different fluids (three with no crystals, one with betamethasone crystals, four with calcium pyrophosphate dihydrate (CPPD) crystals and four with monosodium urate monohydrate [urate] crystals) were examined by all six laboratories. Four laboratories performed well (10 or more correct out of 12) but two did poorly (50% or less correct). False positive crystal identification occurred in eight of 72 samples, but all false positive reports were from two laboratories. CPPD and urate crystals were missed in seven of 24 (29%) and five of 24 (21%) samples respectively. The standard of synovial fluid examination for crystals in Sydney teaching hospitals is not uniform and in some cases appears unsatisfactory.

Betamethasone↗

Inorganic pyrophosphate generation from adenosine triphosphate by cell-free human synovial fluid.

OBJECTIVE: To quantify inorganic pyrophosphate (PPi) production from extracellular adenosine triphosphate (ATP) by human synovial fluids (SF). METHODS: Serial measurements of ATP hydrolysis rate (t1/2) were performed by the luciferase method from a starting concentration of 500 nM in 21 pathologic and one normal cell-free SF samples incubated under physiologic conditions. ATP was then pumped into a sample of each fluid, using the rate constant derived from the t1/2 of that fluid, to provide steady state levels simulating those reported in SF. Trace [32P] gamma ATP was added at the start of the infusion; conversion to [32P] Pi and to [32P] PPi was determined by precipitation of Pi as reduced phosphomolybdate before and after treatment with yeast inorganic pyrophosphatase. Finally, the pumping experiment was repeated and PPi production was calculated from direct measurement of PPi at time zero and at 60 min. PPi hydrolysis was measured in each fluid by [32P] Pi precipitation from [32P] PPi tracer added at time zero. RESULTS: ATP was hydrolyzed by all SF. The mean t1/2 (seconds) in 8 osteoarthritis (OA) samples was 72 s, in 5 calcium pyrophosphate dihydrate (CPPD) 30 s (p < 0.02), in 3 rheumatoid arthritis (RA) 1160 s, in normal 86 s, in 3 olecranon bursal (OB) 54 s, and in 2 total knee replacement fluid samples 17 and 121 s. The major product of ATP hydrolysis was PPi in all but 2 fluids (1 RA, 1 OB), even at lower than steady state levels. At simulated in vivo steady state ATP levels, mean conversion of APT to PPi was stoichiometric in OA and CPPD fluids. PPi hydrolysis was < 4% in all noninflammatory fluids. CONCLUSION: PPi is the major product of extracellular ATP catabolism in most SF. Hydrolysis rates were significantly faster in SF containing CPPD crystals. Mean PPi production by these fluids at simulated in vivo steady state levels was 6-fold that of OA SF (p < 0.01). Hydrolysis of extracellular ATP by ectonucleotide pyrophosphohydrolases can account for all PPi produced by joint issues previously estimated from [32P] PPi pool and turnover studies in human knee joints.

Adenosine Triphosphate↗

Calcium crystal deposition in cervical ligamentum flavum: CT and MR findings.

We report three patients with calcium pyrophosphate dihydrate crystal deposition disease within the ligamenta flava of the cervical spine who presented with progressive myelopathy. Plain radiography showed oval calcified nodules at the level of C4-C5 and C5-C6. On computed myelography, oval calcified nodules were seen in the ligamenta flava of the posterior cervical spinal canal compressing the dural sac. Magnetic resonance revealed oval corresponding hypointense foci both on T1-and T2-weighted images. In two cases, the cervical cord showed hyperintensity at the compression site on T2-weighted images.

Aged↗

Stain removal efficacy of two new fluoride dentifrices containing essential oils.

PURPOSE: To assess in vitro the stain removal efficacy of two new antiplaque/antigingivitis dentifrices utilizing a modification of a previously validated Stookey method. MATERIALS AND METHODS: The modifications to the original Stookey method are the following: (1) study design; three 5 x 5 Latin Squares were employed to minimize bias stemming from position or test run in the study. (2) statistical success criteria; a test formulation was judged to be effective if the lower one-sided 95% confidence limit was "equal to or higher than" 50 since a minimum PCR (pellicle cleaning ratio) score of 50 is needed for a dentifrice to show clinical efficacy. The two test dentifrice formulations contained a fluoride source, a silica abrasive system, and four essential oils. The ADA reference abrasive material (calcium pyrophosphate) and placebo toothpaste were included as positive and negative controls, respectively. RESULTS: Compared to the negative control, the positive control exhibited a statistically higher PCR score; therefore, the validity of this modified Stookey method was confirmed. Additionally, the lower limits of the one-sided 95% confidence interval for the two dentifrice formulations were above the threshold PCR of 50; therefore, this modified Stookey method should predict that both essential oil-containing dentifrices possess acceptable stain removal power.

Analysis of Variance↗

Studies into the association between leucocyte accumulation and oedema formation.

We have treated rats with methotrexate to reduce their circulating leucocyte numbers and in particular their polymorphonuclear leucocytes. Injection of zymosan, calcium pyrophosphate dihydrate crystals, carrageenan or dextran into rat pleural cavities induced leucocyte accumulation and oedema formation both of which were reduced by prior methotrexate treatment. The observation that the depletion of circulating leucocytes reduces both inflammatory cell accumulation and oedema formation suggests that these two processes are closely linked. In contrast treatment of animals with the anti-complementary agent K76COONa blocked leucocyte accumulation but had no effect on oedema formation indicating the two processes can occur independently. This conflicting data suggests that the association between leucocyte accumulation and oedema formation is complex.

Animals↗

Synovial fluid crystals in osteoarthritis.

Apatite crystals, calcium pyrophosphate dihydrate crystals, or both were observed in knee joint effusions from 60% of 100 consecutive osteoarthritis (OA) patients. Crystals were mor common in patients with more severe OA and in joints that had received previous intraarticular steroid injections. Whether the latter was predominantly related to an effect of the steroid or to the fact that steroids were used in more severe cases was not clear. Crystals existed in many effusions without elevated synovial fluid leukocyte counts. A subgroup of 7 patients had both types of crystals, more crystal phagocytosis, and more severe OA.

Aged↗

In vitro and in vivo effects of gold salts on chemotaxis and random migration of rat polymorphonuclear leucocytes.

The effect produced by three gold salts (sodium aurothiomalate, allochrysine, auranofin) on chemotaxis and random migration of rat polymorphonuclear leucocytes (PMN) was investigated under various experimental conditions. The drug activity was examined after incubation in vitro or after administration in vivo. PMNs were recruited after the induction of two acute inflammatory reactions (pleurisies induced by isologous serum or a suspension of calcium pyrophosphate (CaPP) crystals). The three gold salts administered in vivo and in vitro inhibited the chemotactic responses of the two cell types. This action was dose-dependent. Auranofin was the most effective substance while sodium aurothiomalate was the least. The random migration was not always significantly depressed especially for CaPP-elicited cells. Reduction in neutrophil chemotaxis might be an important additional mechanism in the action of gold salts and their activity on inflammatory PMNs recruited at inflammatory foci might be beneficial in the treatment in rheumatic diseases in which PMN migration would be implicated.

Animals↗

Evidence for a promoter of urate crystal formation in gouty synovial fluid.

The effect of serum and synovial fluid obtained from six healthy subjects and from 12 patients with gout, six with rheumatoid arthritis and 18 with calcium pyrophosphate dihydrate arthropathy (CPPD) on the rate of in vitro urate crystal formation was measured. Gouty and normal serum produced similar results. Gouty synovial fluids promoted urate crystal formation significantly more than did rheumatoid or CPPD fluids. The promotion of urate crystal formation by gouty synovial fluid was not due to native urate crystals nor to an effect on the level of urate supersaturation. The development of gout in some, but not other, hyperuricaemic subjects may relate to the presence of promoters (or relative lack of inhibitors) of urate crystal formation in the group who develop gout.

Adult↗

[A case of myelopathy caused by calcified nodules of cervical ligamentum flavum].

A case is reported of a 71-year-old female with cervical myelopathy caused by calcified nodules in the cervical ligamentum flavum and improved by en bloc laminectomy. The calcified nodules were formed by the deposition of two crystals, hydroxyapatite (HAP) and calcium pyrophosphate dihydrate (CPPD). Light microscopy, scanning electron microscopy, energy dispersive X-ray microanalysis and X-ray diffraction study disclosed that the larger nodule located on the right was composed mainly of HAP in the central part and CPPD in the circumference. On the other hand, the smaller nodule located on the left was composed mainly of CPPD crystal. These findings support the hypothesis that calcification of the ligamentum flavum and CPPD crystal deposition disease in the cervical region are the same entity and the both are merely different aspects of the same entity at different chronological stages.

Aged↗

Mechanisms of cellular interaction with monosodium urate crystals. IgG-dependent and IgG-independent platelet stimulation by urate crystals.

Monosodium urate crystals (MSU) stimulate suspensions of washed platelets or neutrophils. When MSU crystals are coated with IgG, as occurs in plasma, stimulation is markedly enhanced. These studies which use MSU-induced human platelet serotonin secretion as a model examine the nature of cellular recognition mechanisms for MSU crystals and IgG-coated MSU crystals. F(ab')2 fragments of specific anti-Fc antibody blocked and the lipopolysaccharide of Salmonella minnesota R595 enhanced human platelet secretion induced by IgG-coated urate crystals. These agents had little effect on stimulation by uncoated crystals. This indicated that urate crystals stimulate platelets independently of fluid phase IgG. Urate crystals directly stimulated suspensions of washed rabbit platelets which lack Fc receptors. In contrast to human cells, stimulation was blocked by IgG. This again demonstrated IgG-independent cell stimulation by urate crystals. Calcium pyrophosphate dihyrate crystals could trigger human platelet secretion only when coated with IgG. This suggests that when crystals are coated with IgG, the surface-bound IgG alone may be the stimulus to the cell. This was supported by the finding that polyvinylpyridine-N-oxide, a hydrogen acceptor, blocked human platelet stimulation by uncoated, but not IgG-coated, urate crystals. These data indicate that urate crystals (and potentially other surface or particles) can stimulate a mediator cell by at least two mechanisms: by direct stimulation without the mediation of adsorbed IgG or, when coated with IgG, by triggering the cell via immunoglobulin receptors.

Blood Platelets↗

The effects of levan on the acute inflammatory response.

The fructose polymer levan has been shown to affect the accumulation of leucocytes in inflammatory lesions. The present study has investigated the effect of levan on experimental pleurisy induced by carrageenan and calcium pyrophosphate dihydrate (CPPD) crystals. Total pleural polymorphonuclear leucocyte counts and exudate volumes were significantly reduced by levan treatment. We were, however, unable to detect any effect on mononuclear cell numbers. Furthermore, levan treatment significantly reduced peripheral leucocyte numbers. The counter-irritant activity of levan was compared with that of a known counter-irritant, dextran. The ability of levan to reduce pleural polymorph numbers and exudate volume could not be accounted for totally by counter-irritation. Studies using an in-vitro leucocyte adhesion assay system indicate that levan affects leucocyte adhesion to vascular endothelium.

Animals↗

[Acute cervical syndrome in chondrocalcinosis. 3 elderly patients with calcifications of the transverse atlantis ligament].

Articular chondrocalcinosis, or pseudogout, is characterized by the deposition of calcium pyrophosphate dehydrate (CPPD) crystals. Vertebral involvement in CPPD crystal deposition disease is known and includes in particular the ligamentum flavum, the posterior longitudinal ligament and the intervertebral disc. We report on 3 elderly patients with peracute cervical syndrome. Plain radiographs showed the usual degenerations. Computerized tomography scans revealed a calcified transverse atlas ligament. The erythrocyte sedimentation rate was elevated. Plain radiographs showed chondrocalcinosis of the hands and knees. The symptoms subsided after 2 days' therapy with antiinflammatory drugs. We conclude that chondrocalcinosis may often be an undetected cause of acute cervical vertebral pain in the elderly patient.

Aged↗

Lack of association between hypothyroidism and chondrocalcinosis.

The association between hypothyroidism and calcium pyrophosphate dihydrate deposition disease (CPPD) is controversial. We studied the prevalence of chondrocalcinosis, the roentgenographic marker of CPPD by obtaining anteroposterior knee roentgenograms in 49 hypothyroid patients over the age of 40 years, and compared them with knee roentgenograms in 31 euthyroid patients matched for age and sex. Only 2 hypothyroid patients and one euthyroid control had knee chondrocalcinosis. Our results indicate that hypothyroid patients have no greater prevalence of chondrocalcinosis compared to euthyroid subjects. There are also no difference in the degree and prevalence of osteoarthritis between the 2 groups, although hypothyroid patients may have a higher prevalence of periarticular osteopenia.

Adult↗

Extrusion of pyrophosphate into extracellular media by osteoarthritic cartilage incubates.

The distribution of calcium pyrophosphate mineral phase, almost exclusively confined to articular cartilage in chondrocalcinosis, and the high level of pyrophosphate (PPi) ion relative to serum in synovial fluid in patients with either chondrocalcinosis or advanced osteoarthritis led to an investigation of whether cartilage cells elaborate PPi ions. Incubates of articular cartilage from young rabbits but not from mature rabbits, as well as growth plates cartilage, released PPi into incubation media during a 4h period. Control rabbit ear cartilage and synovial membrane elaborated negligible amounts of PPi. The PPi was shown to be undialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis, a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. It is postulated that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites are the source of the PPi in such osteoarthritic cartilage. It is further hypothesized that this PPi output accounts at least in part for the elevated PPi levels found in synovial fluid of patients with osteoarthritis.

Alkaline Phosphatase↗