Paul B. Halverson

Phagocytosis of Hydroxyapatite or Calcium Pyrophosphate Dihydrate Crystals by Rabbit Articular Chondrocytes Stimulates Release of Collagenase, Neutral Protease, and Prostaglandins E2 and F2α

Abstract Synthetic hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD) microcrystals are phagocytosed by rabbit articular-cartilage chondrocytes in primary culture. The ingestion of crystals greatly stimulated the release of collagenase, neutral protease, and prostaglandins E2 and F2α into the ambient medium. Lactate dehydrogenase was not released by either crystal despite electron microscopic evidence of cell damage by HA crystals (partial loss of phagolysosomal membrane and increased myelin figures). HA, but not CPPD crystals, stimulated release of/3-glucuronidase. HA crystal concentrations from 50 to 200 μg ml–1 induced a dose-dependent release of collagenase and of extracellular protein. Both phagocytosis and collagenase release were greatly attenuated when HA crystals were added to the chondrocyte monolayers in the absence of serum. As HA and CPPD crystals have been identified in human articular cartilage in association with degenerative changes, it is possible that the cell-crystal interaction described here may be pathogenetically important.

Rhabdomyolysis and Renal Failure in Hypothyroidism

Excerpt Muscle involvement is a frequent manifestation of hypothyroidism (1, 2). Findings include myalgias, stiffness, weakness, elevated muscle enzymes, electromyographic abnormalities, and histol...

Histopathological and ultrastructural studies of synovium in Milwaukee shoulder syndrome--a basic calcium phosphate crystal arthropathy.

Light and electron microscopic study of synovial specimens from four patients with the Milwaukee shoulder syndrome disclosed vascular congestion, villous and focal synovial lining cell hyperplasia, occasional giant cells, and fibrin deposition both within and on the surface of the synovium. Although these changes are non-specific, the finding of basic calcium phosphate crystal aggregates in all four cases and the near total absence of an inflammatory reaction are helpful in distinguishing this condition from other types of arthritis. The focal areas of synovial cell hyperplasia may relate to the powerful mitogenic effect of both synthetic and naturally occurring calcium-containing crystals in concentrations found in the synovial fluid of these patients.

Clearance of calcium pyrophosphate dihydrate crystals in vivo

The clearance rate of isotopically labeled synthetic triclinic calcium pyrophosphate dihydrate (CPPD) crystals injection into rabbit joints was estimated by serial counting. Kinetic analysis using a four compartment model showed that half of the injected dose was cleared from 4 rabbit knee joints in 19.1 +/- 0.42 (SEM) days. Profound hypomagnesemia, produced in 2 rabbits with a low magnesium diet, did not affect the rate of crystal clearance detectably. Lavage of joints with solutions known to promote CPPD crystal solubility failed to remove detectable radioactivity. The previous finding of CPPD crystals in synovial phagocytes by electron microscopy, together with the finding of nuclide activity in the synovium and the failure to remove such activity by joint lavage, suggests that endocytosis by synovial cells is an important, effective mechanism controlling the synovial fluid concentration of crystals in patients with CPPD crystal deposition disease.

Accelerating the Production and Application of Evidence for Public Health System Improvement: the Search for New Frontiers

The new journal Frontiers in Public Health Services and Systems Research provides a platform for rapidly and widely communicating emerging findings and lessons learned from studies of public health services and delivery systems.

The effect of hydroxyapatite crystallinity on hemolysis.

SummaryCrystalline hydroxyapatite is a component of bone, teeth, and numerous pathological calcifications. The apatite crystal structure can accommodate a wide variety of atomic substitutions which gives apatite crystals an unusually high degree of variability in biochemical and physical properties. Apatite crystallites interact with numerous cellular systemsin vivo, and some of these interactions may lead to altered cellular function. One measure of crystal-membrane interactions is crystal-induced membranolysis of human red blood cells. Hemolytic potentials at constant crystal surface areas were measured at 1, 2, and 4 hours for 29 different preparations of apatite. Each apatite sample was characterized by its morphology, particle size, % CO3, zeta potential, and broadening of the (211), (112), (300), (202), and (002) diffraction maxima. Only the surface area/g and the X-ray powder diffraction line broadening showed a significant inverse correlation with hemolytic potential. These parameters were related to each other, and are indications of the degree of crystallinity.

Simultaneous occurrence of calcium pyrophosphate dihydrate and basic calcium phosphate (hydroxyapatite) crystals in a knee.

An 82-year-old man developed periarticular roentgenographic calcifications of the knee joint. Fragments of meniscus and peritendinous tissue were collected during total knee arthroplasty. Crystals were released from tissues by collagenase digestion. Calcium pyrophosphate dihydrate crystals were identified in the meniscus, and basic calcium phosphate crystals were identified in the peritendinous tissue. Methods of crystal identification included compensated polarized light microscopy, scanning electron microscopy with X-ray energy dispersive analysis, and X-ray diffraction.

“Milwaukee shoulder” syndrome: Microspherules containing hydroxyapatite, active collagenase and neutral protease in patients with rotator cuff defects and glenohumeral osteoarthritis

Abstract A new syndrome involving the shoulder joints is described, associating HA crystals in microspheroids, active collagenase, neutral protease with destruction of the fibrous rotator cuff and glenohumeral osteoarthritis. This pathogenetic mechanism postulated for this destructive arthropathy may have applicability for the devolutionary joint changes associated with other microcrystals found in joints and almost certainly applies to other joints besides the shoulder.

Triple crystal disease: monosodium urate monohydrate, calcium pyrophosphate dihydrate, and basic calcium phosphate in a single joint.

A 49 year old man is described with a polyarticular arthritis. Synovial fluid aspirated from the knee joint showed monosodium urate monohydrate and calcium pyrophosphate dihydrate by polarised light microscopy. Additionally, diphosphonate binding and scanning electron microscopy with energy dispersive analysis showed that basic calcium phosphate crystals were also present. This appears to be the first report of three crystals occurring simultaneously in a single joint.