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Biomedical subjects

P B Halverson

Publications and source records attributed to P B Halverson.

34 records · Page 2Linked to original sources

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.

Aged↗

Crystal populations in human synovial fluid. Identification of apatite, octacalcium phosphate, and tricalcium phosphate.

Defatted joint fluid pellets from 4 patients with the "Milwaukee shoulder" syndrome, an aspirate of milky fluid from subcutaneous tissue of a girl with dermatomyositis/calcinosis, and 2 rabbit synovial membranes calcified by calciphylaxis were studied by Fourier transform infrared analysis. This method permits sequential electronic subtraction ("stripping") of known patterns of highly characterized reference compounds from an unknown sample pattern. Collagen and hydroxyapatite, with carbonate partially (1-3%) substituted for phosphate, and to a lesser extent hydroxyl, were found in all samples. Octacalcium phosphate (OCP) was found in all samples except that from a patient with synovial chondromatosis which contained tricalcium phosphate (TCP). Sulfate was found in 2 of the shoulder joint fluid specimens. An unidentified organic phase was present in all samples. This study confirms recent observations by others that pathologic calcifications contain several mineral phases. These data raise the possibility that hydroxyapatite nucleation may be controlled by hydrolytic alteration of precursor calcium phosphate phases such as OCP or TCP. Studies of the biologic effects of synthetic calcium phosphate crystals must take into account the existence of several crystalline phases in natural pathologic calcifications.

Animals↗

Phagocytosis of hydroxyapatite or calcium pyrophosphate dihydrate crystals by rabbit articular chondrocytes stimulates release of collagenase, neutral protease, and prostaglandins E2 and F2 alpha.

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 F2 alpha 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 beta-glucuronidase. HA crystal concentrations from 50 to 200 micrograms 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.

Animals↗

Enzymatic release of microspheroids containing hydroxyapatite crystals from synovium and of calcium pyrophosphate dihydrate crystals from cartilage.

Incubation of minced, focally calcified, chondromatosis tissue obtained at operation from a patient with Milwaukee shoulder (rotator cuff defect and glenohumeral osteoarthritis associated with synovial fluid, hydroxyapatite crystals in microspheroidal masses, collagenase, and neutral protease) with partially purified mammalian synovial cell collagenase released masses of hydroxyapatite crystals of the same size as those originally found in the patient's synovial fluid. Incubation of mineral articular cartilage obtained from a shoulder joint at arthroplasty for a destructive arthropathy in a patient with generalised calcium pyrophosphate dihydrate (CPPD) crystal deposition with partially purified synovial cell collagenase freed CPPD crystals from their matrix. These data are compatible with a previously postulated mechanism linking microcrystals to destructive arthropathies, that is, crystal endocytosis by synovial cells stimulating collagenase secretion with subsequent enzymatic crystal "strip-mining', releasing additional crystals into the synovial fluid in a self-perpetuating cycle.

Calcium Pyrophosphate↗

"Milwaukee shoulder"--association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. I. Clinical aspects.

Four women, aged 63 to 90 years old, presented with mildly painful shoulders of decreased mobility or stability. Radiographic evidence of a complete tear of the fibrous rotator cuff was present in 7 of 8 shoulder joints. Microspheroids containing hydroxyapatite crystals were seen by scanning electronmicroscopy in 12 of 13 synovial fluid samples. All synovial fluids showed activated collagenase and neutral protease activity. This constellation of findings represents a heretofore undescribed syndrome which we have designated "Milwaukee shoulder."

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"Milwaukee shoulder"--association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. II. Synovial fluid studies.

Hydroxyapatite crystals in spheroid-shaped masses 1.9-15.6 micrometer in diameter were found in 12 of 13 synovial fluids obtained from the shoulder joints of 4 patients with rotator cuff tears and glenohumeral osteoarthritis. Two of 16 control joint fluids also showed these particles. Collagen types I, II and III were identified in the joint fluid pellets from 3 of the 4 patients, and fibers with typical collagen periodicity were also seen on transmission electronmicroscopy. Collagenase and neutral protease activities were found in fluids from 5 joints in 3 patients, whereas active collagenase was found in only 1 of 10 fluids from rheumatoid arthritis patients and in none of 3 fluids from patients with osteoarthritis. Neutral protease activities were present in several rheumatoid joint fluids. These findings are compatible with the hypothesis of an enzymatic release of hydroxyapatite crystals from the synovium and endocytosis by synovial macrophage-like cells with subsequent crystal-stimulated release of collagenase and neutral protease into the joint fluid, completing a pathogenetic cycle.

Aged↗

"Milwaukee shoulder"--association of microspheroids containing hydroxyapatite crystals, active collagenase, ad neutral protease with rotator cuff defects. III. Morphologic and biochemical studies of an excised synovium showing chondromatosis.

Synovial tissue excised from the unstable right shoulder joint of a patient with an absent rotator cuff, severe glenohumeral joint degeneration, and hydroxyapatite-containing microspherules, collagen types I, II, and III, active collagenase, and neutral protease in the joint fluid showed extensive osteochondromatosis histologically. Electronmicroscopy revealed calcific foci in microvilli which could easily escape into the adjacent joint space through areas denuded of synovial cells. Fibrocytes demonstrated intensive pinocytotic activity of unknown significance. Energy dispersive analysis showed elemental ratios consistent with hydroxyapatite. A literature review suggested some relationships between the various pathologic lesions present in this joint. Whether similar synovial changes exist in the opposite shoulder joint of this patient and in 3 other subjects with nearly identical clinical, radiographic, and joint fluid findings is not known.

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Release of collagenase, neutral protease, and prostaglandins from cultured mammalian synovial cells by hydroxyapatite and calcium pyrophosphate dihydrate crystals.

Hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD) crystals were phagocytosed when added to cultured human rheumatoid or normal canine synovial cells. Collagenase and neutral protease secretion into the culture medium was increased 5- to 8-fold over control values in the presence of HA and increased 3-fold in the presence of CPPD crystals. HA but not CPPD crystals induced a 300-fold increase in human rheumatoid synovial cell culture fluid prostaglandin (PG) E2 levels and an 8-fold increase in PGF alpha levels. This mechanism may be important in the pathogenesis of the destructive arthropathies associated with HA and CPPD crystals.

Animals↗

Identification of hydroxyapatite crystals in synovial fluid.

A semiquantitative technique employing (14C) ethane-1-hydroxy 1, -1-diphosphonate (EHDP) binding has been used to detect crystals, presumably hydroxyapatite, in human synovial fluid samples which were handled to prevent the formation of artifactual mineral phase. Binding material was found in 29% of non-inflammatory and in none of inflammatory joint fluids. Nuclide binding material was strongly correlated with the presence of CPPD crystals and with radiographic evidence of cartilaginous degeneration.

Adult↗

Clearance of calcium pyrophosphate dihydrate crystals in vivo. I. Studies using 169Yb labeled triclinic crystals.

Synthetic triclinic calcium pyrophosphate dihydrate crystals were uniformly trace-labeled with Ytterbium-169 (169Yb), a pure gamma-emitting isotope with a halflife of 31 days. The solubility of the labeled crystals was similar to that of cold synthetic crystals. The clearance rate of labeled sterile crystals, sieved to obtain the desired size, was determined after injection of microgram quantities into 4 arthritic huuman and 3 normal adult rabbit joints and corrected by the observed rate of clearance of free 169Yb. The derived rate constants were then used to calculate the time required for half of the injected dose of CPPD to be cleared from the joint. Crystal clearance was found in all instances. Crystal removal from normal rabbit joints was much more rapid than from the much larger human arthritic joints and was inversely proportional to the size of the crystals injected.

Animals↗

Toxicity of penicillamine. A serious limitation to therapy in rheumatoid arthritis.

A retrospective study of penicillamine toxicity in 156 patients yielded a high incidence of toxic reaction (62%), necessitating discontinuation of the drug therapy in 36% of the patients. Of the total group, proteinuria occurred in 14%, hematologic toxic reaction in 11%, mucocutaneous toxic reaction in 28%, and gastrointestinal intolerance in 12%.

Adult↗

Systemic lupus erythematosus: medical and nursing treatments.

Systemic lupus erythematosus is a multisystem autoimmune disease that may affect skin, joints, mucous membranes, heart, lungs, kidneys, nervous system and all the blood cell lines. Although its cause is unknown, abnormal immune function results in the formation of antibodies directed against various components of the human body (autoantibodies). Treatment depends of the severity of the illness and may include nonsteroidal antiinflammatory agents for arthritis; antimalarial therapy for skin disease and other mild lupus manifestations; and corticosteroids and immunosuppressive agents including azathioprine, cyclophosphamide, and methotrexate for more severe lupus manifestations. Persons affected by lupus and their families need help in understanding the condition and require support as they deal with fear, depression, and possible disability. Implications for nursing are varied and include patient/family education about medication, joint protection principles, energy conservation, pain and stress management, and coping techniques.

Female↗

Extraarticular manifestations of rheumatoid arthritis.

Rheumatoid arthritis affects joints and other systems in the body. Dryness of the eyes and mucous membranes are referred to as Sjogren's Syndrome. The heart is usually spared but the lungs can be affected by pleurisy, scarring, and the formation of nodules in the lungs. The nervous system may be involved by compression neuropathy (e.g. carpal tunnel syndrome), peripheral neuropathy, or occasionally from cervical cord compression. The rare complication of vasculitis (inflammation of blood vessels) may be devastating because of gangrene or severe internal organ damage. Some of the effects of rheumatoid arthritis may be "invisible" such as anemia or abnormalities in the white blood cell count. Osteoporosis is usually asymptomatic until a fracture occurs.

Arthritis, Rheumatoid↗

The spondyloarthropathies.

The spondyloarthropathies represent a heterogeneous group of arthropathies including ankylosing spondylitis, reactive arthritis with Reiter syndrome as one subtype, arthritis associated with inflammatory bowel disease, arthritis associated with psoriasis, and juvenile spondyloarthritis. These conditions are linked by several common features: inflammatory arthritis involving the back, a high prevalence of HLA-B27, frequent tendon/ligament insertion inflammation, and several common extra-articular manifestations (iritis, skin lesions). Although not uncommon, these types of arthritis are more difficult to recognize than other types of arthritis such as osteoarthritis and rheumatoid arthritis.

Adult↗

Nonsteroidal antiinflammatory drugs: benefits, risks, and COX-2 selectivity.

Nonsteroidal antiinflammatory drugs (NSAIDs) are the most frequently prescribed class of medication for arthritis and other musculoskeletal disorders. NSAIDs block prostaglandin production, thereby reducing pain and inflammation, but may also cause significant side effects, particularly ulcers in stomach and duodenum. Some risk factors include age, previous history of ulcer, and high dose of NSAID. Synthetic prostaglandins, H2 blockers, and proton pump inhibitors have been employed to reduce risks with varying degrees of success. New NSAIDs that block only prostaglandins at sites of inflammation (COX-2 selective NSAIDs) may be significantly safer than traditional NSAIDs.

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