Adaptations for marine habitat and the effect of Triassic and Jurassic predator pressure on development of decompression syndrome in ichthyosaurs.

Decompression syndrome (caisson disease or the "the bends") resulting in avascular necrosis has been documented in mosasaurs, sauropterygians, ichthyosaurs, and turtles from the Middle Jurassic to Late Cretaceous, but it was unclear that this disease occurred as far back as the Triassic. We have examined a large Triassic sample of ichthyosaurs and compared it with an equally large post-Triassic sample. Avascular necrosis was observed in over 15% of Late Middle Jurassic to Cretaceous ichthyosaurs with the highest occurrence (18%) in the Early Cretaceous, but was rare or absent in geologically older specimens. Triassic reptiles that dive were either physiologically protected, or rapid changes of their position in the water column rare and insignificant enough to prevent being recorded in the skeleton. Emergency surfacing due to a threat from an underwater predator may be the most important cause of avascular necrosis for air-breathing divers, with relative frequency of such events documented in the skeleton. Diving in the Triassic appears to have been a "leisurely" behavior until the evolution of large predators in the Late Jurassic that forced sudden depth alterations contributed to a higher occurrence of bends.

Avascular necrosis: occurrence in diving cretaceous mosasaurs.

A study of vertebrae of extinct giant marine lizards showed the presence of avascular necrosis in two of the three most common genera of these mosasaurs, Platecarpus and Tylosaurus. This bone disease was invariably present (involving 5 to 66% of vertebrae) in these genera, but absent in a third genus Clidastes. Differential occurrence of avascular necrosis may be related to decompression syndrome, suggesting different habitat and diving habits of the respective genera.

Symmetrical erosive peripheral polyarthritis in the Late Archaic Period of Alabama.

Rheumatoid arthritis was first described unambiguously in 1800, but its etiology and historical origins are still obscure. Definite rheumatoid arthritis has not been demonstrated in pre-19th century Old World skeletal remains. Six individuals who lived 3000 to 5000 years ago in northwestern Alabama and present erosive polyarthritis characteristic of rheumatoid arthritis are described. The diagnosis raises the possibility that rheumatoid arthritis can be associated with a New World pathogen or allergen.

Hematologic perturbations associated with salicylate.

Interactions of salicylates with the hematopoietic system are reviewed. Development of anemia is discussed with respect to fluid retention, gastrointestinal bleeding, and hemolytic anemia. Alterations in polymorphonuclear leukocyte and platelet function are evaluated. Interactions with anticoagulants and with the coagulation system are identified.

Appendix: a model of plaque formation.

Equations describing plaque formation in soft agar have been based on certain simplifying assumptions, for which data are presented. The derived equations permit one to calculate (i) average plaque size as a function of the initial density of indicator cells (Do), (ii) the number of cells lysed per plaque as a function of Do, and (iii) the cumulative number of cells lysed at various stages of plaque development. The calculated values agree well with those determined experimentally.

Lymphadenopathy and lymph node infarction in the course of gold therapy.

Lymphadenopathy, as a complication of gold therapy, appears to be an uncommon occurrence. Lymph node infarction has not been previously documented in this setting. The unique pathologic features in this case may reflect: a phenomenon specific to gold; early examination of the infarcted node; or underlying leukocytoclastic angiitis secondary to gold toxicity. Polymorphonuclear leukocytic infiltration of an infarcted lymph node has apparently not been previously reported.

Calcaneal abnormalities and erosive bone disease associated with sickle cell anemia.

Although the arthritis of sickle cell anemia has generally been considered noninflammatory, published studies suggest the existence of an inflammatory variety. The common association of bone abnormalities with inflammatory arthritis precipitated a radiographic evaluation of 100 patients, chosen at random from those followed at the University of Tennessee Sickle Cell Center. Erosive disease was identified in 14 percent. This was correlated with clinical manifestations in a longitudinal manner. Loss of definition of the cortical margin in the superior aspect of the calcaneus appears to be erosive in nature. It has not been observed previously and may be pathognomonic for sickle cell anemia. Arthrographic and gross pathologic material is presented in support of this hypothesis.

Spondyloarthropathy as an Old World phenomenon.

The presence of spine and sacroiliac involvement and the nature and distribution of erosive lesions allowed definitive diagnosis of spondyloarthropathy in the great apes (Gorilla and Pan [chimpanzee]), the lesser ape (Hylobates), and Old World monkeys (Theropithecus, Papio, Cercopithecus, Macaca, Colobus, Presbytis, and Erythrocebus). Analysis of lesional character, distribution, radiological appearance, and sex ratios showed a picture indistinguishable from human spondyloarthropathy. This contrasts with orangutans (Pongo), who lack reactive bone or sacroiliac involvement. A different pathophysiology, as yet undefined, is implied for their erosive arthritis. Limited individual susceptibility to spondyloarthropathy in humans (1% to 4%), Old World monkeys (2.4%), and lesser apes (2.4%) contrasts with the high frequency of disease in the great apes (20% to 28%). The wide geographic distribution of this phenomenon suggests an African and perhaps Asian "panendemic." This natural disease state provides a unique model for in-depth analysis of the contribution of genetic and environmental factors to disease pathophysiology.

Pathogenesis of rheumatoid arthritis: a vascular hypothesis.

Past research into the pathogenesis of RA has generally concerned itself with established inflammation. The present review summarizes alterations in microvascular anatomy and function which occur during the hypoxic state, in various experimental and disease conditions. It further shows that tissue hypoxia is a common finding in RA and that the microvascular alterations of RA are similar to those produced by experimental hypoxia. The available data suggest that microcirculatory compromise, concomitant with an increase in metabolic needs of synovial tissue, may initiate tissue injury via anoxia and acidosis, resulting in hydrolytic enzyme release, increased vascular permeability and acceleration of inflammatory processes. It is further believed that the microcirculatory abnormality may be generalized, accounting for the systemic manifestations often seen in RA. Factors effecting arteriolar blood flow obstruction are reviewed to identify areas for future investigation in RA and other disorders involving microvasculopathy. The multitude of longknown and newly recognized factors predisposing to vasospasm and vasodilatation have been outlined as a guide to possible mechanisms which may be operative in RA. An attempt has been made to gather and synthesize the available data in the hope that it may stimulate other investigators to pursue more definitive research into specific areas which may show early microvascular abnormalities in the pathophysiology of RA. Identification of factors operative early in the pathogenesis of RA, before it becomes self-perpetuating, may well be a step in the direction of preventing the ravages of this disease, or providing insight to more effective control.

Dactylitis: implications for clinical practice.

OBJECTIVES: To assess the specificity of dactylitis for the diagnosis of spondyloarthropathy, sarcoidosis, and gout; and to characterize dactylitis specifically associated with gout. METHODS: Dactylitis was prospectively assessed among all individuals presenting to the Arthritis Center of Northeast Ohio from 1986 to 1996. RESULTS: Dactylitis was observed in 12% of individuals with spondyloarthropathy, 17% with sarcoidosis, and 5% with gout, but not in 96 patients with rheumatoid arthritis or in 2,434 patients with osteoarthritis, neck or back pain, or collagen vascular diseases. Among individuals with spondyloarthropathy, dactylitis was present in 22% with psoriatic, 28% with Reiter's syndrome, and only 7% with undifferentiated spondyloarthropathy. Gouty dactylitis was found only in individuals with polyarticular disease. CONCLUSIONS: Dactylitis is a valuable clue in the differential diagnosis of arthritis. Compared with the wider spectrum in children, sausage-shaped digits have only a few known causes in adults: Reiter's syndrome, psoriatic arthritis, sarcoidosis, flexor tendon sheath infections, and gout. In our series, the presence of dactylitis eliminated rheumatoid arthritis from the differential diagnosis.

Skeletal survey of Cayo Santiago rhesus macaques: osteoarthritis and articular plate excrescences.

OBJECTIVES: This study was performed to complement studies on spondyloarthropathy in rhesus macaques by quantifying and characterizing another major form of arthritis and contrasting it with osteoarthritis. METHODS: Skeletons of 269 macaques of known age and troop affiliation from the free-ranging Cayo Santiago colony (Caribbean Primate Research Center) were macroscopically surveyed for the presence of articular changes of osteoarthritis, articular plate excrescences, and calcifications that project back over the joint surface in all diarthrodial joints. Statistical tests were used to establish the independence of pathological conditions, age, gender, troop membership, and specific joint involvement. RESULTS: Subchondral articular surface excrescences or calcific plate-like articular surface overgrowth were noted in 17% and osteoarthritis in 18% of Cayo Santiago macaques. Distribution of joint involvement and sex ratio (1:1) of the former condition were independent of either troop membership or the distribution of osteoarthritis. CONCLUSION: Three major forms of arthritis are common in rhesus macaques: osteoarthritis, spondyloarthropathy, and a category that might be referred to as apical plate excrescences (APE). The latter is very different from spondyloarthropathy, rheumatoid arthritis, osteoarthritis, gout, and infectious arthritis. It is quite similar to what in the past has been referred to as the radiographic form of calcium pyrophosphate deposition disease (CPPD) in humans. A new name has not been offered for the identification/categorization of this phenomenon in dry bone. Its occurrence in rhesus macaques appears to present a natural model for characterization of genetic, immunologic, and environmental aspects of this phenomenon. The acronym APE is offered for consideration in naming this category of arthritis in skeletal material.

Geographic distribution of rheumatoid arthritis in ancient North America: implications for pathogenesis.

The fifth centennial of Columbus stimulates renewed interest in New World origins of disease. The earliest documentation of rheumatoid arthritis was in the New World. Subsequent study of its distribution in the New World in antiquity defines localization to a very specific geographic region. The absence of rheumatoid arthritis in 63 archaeological sites surrounding the original "catchment area" and in five Old World sites, with documented spread over time, suggests that it is a vector (microorganism or allergen)-transmitted disease.

Radiologic assessment of bone and joint disease. I. Magnification radiology.

The advantages and limitations of magnification techniques are presented. Optical and geometrical techniques each have their proponents. The geometrical technique has proven valuable in the assessment of trauma, metabolic bone disease, arthritis, osteomyelitis, and neoplasm. It often shows pathology inapparent on conventional radiographs.

Reflex sympathetic dystrophy.

Reflex sympathetic dystrophy, causalgia, Sudeck's atrophy, shoulder-hand syndrome, and transient osteoporosis represent a spectrum of sympathetic disturbances which typically present with regional findings. They are often pauciarticular in distribution and uniquely sensitive to timely therapeutic intervention and to preventative measures. Clinical and radiologic appearances are quite characteristic. Thermographic examination provides a valuable tool for monitoring the therapeutic response. The major factor in therapeutic efficacy is aggressive physical therapy. Although therapeusis has been facilitated by a multitude of agents, therapeutic resistance is unfortunately the circumstance, when intervention is delayed.

Synovitis equivalent to erosions in rheumatoid arthritis: implications of skeletal analysis for the clinical management of contemporary rheumatoid arthritis.

Examination of a contemporary skeletal collection revealed a rheumatoid subgroup with parameters mirroring those of contemporary clinical populations. This rheumatoid population was also indistinguishable from contemporary (live) clinical populations, on the basis of the actual distribution of radiologically detectable erosions, thus validating its representativeness. Gross examination of these defleshed skeletons allowed assessment of the significance of erosive disease in rheumatoid arthritis. As anticipated, the frequency of visibly detectable erosions exceeded that detectable radiologically. The frequency of visibly detectable erosions, however, was indistinguishable from the frequency of synovitis in clinical populations. The excellent correlation of the gross and clinical distribution of disease suggests that some degree of erosive disease is integral to all lesions of rheumatoid arthritis and that only the relative insensitivity of radiologic techniques precludes universal recognition of those erosions. This work suggests that any therapeutic intervention which settles for only partial synovitis control will not prevent the progression of erosive disease; and perhaps explains the difficulty of demonstrating alterations in erosion progression in studies of disease modifying agents.

Geographic distribution of calcium pyrophosphate (CPPD) deposition disease in pre-Columbian North America: independent validation of CPPD criteria.

Calcium pyrophosphate deposition disease (CPPD), a form of crystalline arthritis, has a unique distribution in the Early to Middle Archaic Periods (3000 to 8000 years before the present) of North America, contrasting with the generalized geographic distribution of osteoarthritis. Incursion of CPPD into specific regions suggests possible migration patterns. The disparate geographic distribution of CPPD and osteoarthritis provide independent verification of the validity of diagnostic criteria utilized for the identification of CPPD.

Microfoci of avascular necrosis in sickle cell anemia: pathophysiology of the dot dash pattern.

OBJECTIVE: Definition of the nature of calcaneal "erosions" in sickle cell anemia. METHODS: Skeletons of individuals demonstrated to have had sickle cell anemia were examined for the presence of calcaneal surface discontinuity. RESULTS: Calcaneal and articular surface osseous microinfarction were identified macroscopically and confirmed radiologically by CT. CONCLUSIONS: This appears to be the first macroscopic identification of calcaneal and articular surface osseous microinfarction in sickle cell anemia and explains the osseous pathology that appears so unique to sickle cell anemia.

Calcium pyrophosphate deposition disease: description in defleshed skeletons.

The osseous appearance, skeletal distribution, and distinguishing features of calcium pyrophosphate deposition disease (CPPD) were delineated in a population of 2906 contemporary defleshed skeletons. The limitations of routine x-ray and clinical examination were transcended in this study of defleshed bones. The nature of the disease was clearly identified and preconceived notions (based on the "shades of black and white" of the conventional x-ray technique) were examined on the basis of the actual osseous impact. Epidemiologic assessment of this disease allowed it to be distinguished from rheumatoid and other erosive forms of arthritis. Analysis of the "pseudo-rheumatoid" subgroup of CPPD provided clear criteria for distinguishing the disease from rheumatoid arthritis. Characterization of the nature and epidemiology of osseous alterations in a contemporary skeletal population permitted the development of a standard for recognition of CPPD in skeletal populations and for clarification of the nature of associated pseudo-erosions.