Peter A Simkin

Peter A Simkin
University of Washington Seattle | UW · Division of Rheumatology

MD

About

148
Publications
7,359
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Introduction
Peter A Simkin, Professor Emeritus of Medicine at the University of Washington, currently works on 2 hypotheses: #1.sees subchondral compartments of bone with effectively fixed volumes, pressurized fat under impact load, and tensile weight bearing in trabecular walls. #2 sees tidemarks of cartilage as unique depots of chondrocytic debris which may serve as auto-antigens in the pathogenesis of rheumatoid arthritis.
Skills and Expertise
Additional affiliations
July 1966 - present
University of Washington Seattle
Position
  • Emeritus Professor of Medicine

Publications

Publications (148)
Article
Full-text available
Most students of articular mechanics consider impact loads to be compressive forces that are borne by an intraosseous, trabecular scaffold. The possible role of marrow fat, which comprises about 75% of the structure, is generally ignored, and the potential contribution of type 1 collagen, the prototypic tensile protein, is not considered. Here, I q...
Article
In synovial joints, the lining cells do not have tight junctions with their neighboring cells and they have no underlying basement membrane. Therefore, the synovial fluid within the articular cavity is continuous with the interstitial fluid of the synovial intima. These features, combined with ready access to the space via arthrocentesis, permit qu...
Article
Full-text available
Although some readers of The Journal may find the September article by Torres, et al a challenge, we believe the effort to persevere will be well worth it. This is because the report nicely illustrates how the burgeoning field of analysis of common variants in gene sequences (polymorphisms), when combined with scrupulous attention to the clinical c...
Article
Objective: To report our experience with the efficacy and safety of anakinra for acute gouty arthritis in medically complex hospitalized patients. Methods: We reviewed the hospital charts of 26 patients treated with anakinra for crystal-induced arthritis since 2007. Demographics, comorbid conditions, reason for anakinra use, response to treatmen...
Article
Full-text available
Background Urate crystals have been recognized anecdotally in a long list of nonarticular tissues but have not, to our knowledge, been sought or found in inflamed prostate glands. Like gouty arthritis, chronic prostatitis affects middle-aged and older men, and the prostate is often exposed to reflux of highly concentrated uric acid within the urine...
Article
The epidemiology of gout has changed dramatically over the past century. Once thought of as a disease of the nobility, it is now an egalitarian disease that affects patients across the socioeconomic spectrum. The incidence of gout has also risen in recent years, to the point that we are now seeing what is regarded by some as a "second epidemic" of...
Article
Full-text available
As the most conspicuous histologic feature of normal adult articular cartilage, the tidemark begs for our understanding. In their original description, Fawns and Landells likened this landmark to the irregular line of debris that is left on a sandy beach by the high point of a now-receding tide1 (Figure 1A). Such tidemarks comprise a mixture of mar...
Article
Our study uses the entire proteomes of serum and synovial fluid (SF) to characterize the avenues of microvascular egress of plasma proteins, and quantifies that traffic in normal and diseased human knees. Paired aliquots of serum and SF were collected from 17 knees of 11 subjects who died without evident joint disease and 16 patients with clinical...
Article
Basic calcium phosphate (BCP) crystals are common components of osteoarthritis (OA) synovial fluid. Progress in understanding the role of these bioactive particles in clinical OA has been hampered by difficulties in their identification. Tetracyclines stain calcium phosphate mineral in bone. The aim of this study was to investigate whether tetracyc...
Article
Significant gaps persist in our understanding of chondrocyte biology. We do not know when, how, or even whether these cells are replenished throughout the normal, human life span. We are taught that as much as 90% of the cartilage is "metabolically inert" interterritorial matrix, but we do not know how this substance is regularly replaced (as it is...
Article
Nonhuman primates develop the characteristic lesions of osteoarthritis, making them attractive biomedical models for the study of environmental factors, such as diet, which may influence the progress of the condition. We used ELISA assays of potential markers of osteoarthritis which were developed for use in humans to see if we could determined the...
Article
Background Nonhuman primates develop the characteristic lesions of osteoarthritis, making them attractive biomedical models for the study of environmental factors, such as diet, which may influence the progress of the condition. Methods and materials We used ELISA assays of potential markers of osteoarthritis which were developed for use in humans...
Article
Bilirubin metabolism is reviewed and neonatal jaundice of various types is described. The need for quick, accurate tests for unbound, unconjugated bilirubin is discussed in relation to new suggestions that lower levels of this specific portion of bilirubin may cause damage in the newborn The benefits and risks of present treatments are evaluated.
Chapter
A large and growing body of literature attests to the broad, continuing interest in cartilage-derived molecules as “markers” of damage and repair across a wide variety of joint diseases. This chapter aims to put such data in the context of normal and pathologic joint physiology. It introduces important caveats in the interpretation of marker data a...
Article
Full-text available
First identified by the Egyptians in 2640 BC, podagra (acute gout occurring in the first metatarsophalangeal joint) was later recognized by Hippocrates in the fifth century BC, who referred to it as 'the unwalkable disease'. The term is derived from the Latin word gutta (or 'drop'), and referred to the prevailing medieval belief that an excess of o...
Article
Gout is an increasingly common medical problem. The traditional risk factors of male sex and high red meat or alcohol consumption have been joined by a wave of newer risk factors, such as increased longevity, the metabolic syndrome (hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular disease risk), use of diuretics, low-...
Article
Full-text available
According to Wolff's law of bone architecture, the femoral head should contain a robust system of subchondral trabeculae to support the massive loads involved in normal use of the hip. Instead, the trabeculae are slender and become progressively more so as they near the contact surface. This seeming inconsistency may be resolved if the loads are bo...
Article
Intraosseous hypertension has been associated with a deep aching bone pain, particularly at rest, in subsets of patients with osteoarthritis of the hip and knee. The pathophysiology of this problem remains uncertain, but intraosseous phlebography implicates outflow impairment at relatively distal venous sites. Although the issue has been controvers...
Article
Full-text available
Tumour necrosis factor alpha (TNF alpha) antagonists are effective for the treatment of rheumatoid arthritis (RA), but concerns remain about the safety of these agents in the presence of chronic infections, including hepatitis C virus (HCV) infection. To examine the influence of treatment with TNF alpha antagonists on levels of HCV viraemia and ser...
Article
Spinal degenerative disk disease (DDD) in a radiographic, cross-sectional sample of 192 female macaque monkeys, approximately 5-30 years old, is described. The presence and extent of disk space narrowing (DSN) and anterior osteophytosis were assessed with reference to age, average lifetime body mass. and distribution within the thoracolumbar spine....
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Full-text available
Article
In the hip and sacroiliac joints, ankylosing spondylitis attacks the acetabulum over the femoral head and the ilium in preference to the sacrum. Both sites involve inflammation in bone subjacent to fibrocartilage with relative sparing of opposing, hyaline cartilage-surfaced mates. This disease appears to target connective tissues rich in fibrillin-...
Article
Full-text available
Biology of the synovial joint. Eds C W Archer, B Caterson, M Benjamin, J R Ralphs. (Pp 443; £70.) Amsterdam: Harwood Academic Publishers, 1999. ISBN 90-5702-327-X. Biology of the Synovial Joint grew out of a symposium held during the summer of 1996 at the University of Wales in Cardiff. The editors convened that meeting in the “belief that joints...
Article
To evaluate whether extended use of continuous passive motion (CPM) may allay the pain of walking, diminish disease effect, and increase the usual walking speed in patients with osteoarthritis (OA) of the hip. This pilot study comprised 21 patients with Kellgren-Lawrence grade 2-4 OA of the hip who used CPM for periods of 1.2 to 7.6 h daily through...
Article
To investigate the role of the posterior tibial tendon in the flat foot deformity of rheumatoid arthritis (RA). Eleven patients with hyperpronated feet and 9 without hyperpronation underwent magnetic resonance imaging (MRI) of the feet and ankles. Radial oblique double echo images provided cross sectional views of the posterior tibial tendon as it...
Article
Although there continue to be relatively few basic studies of the metabolism and transport of urate, clinical interest in gout and hyperuricemia remains high. A number of interesting new observations are described here from the published literature of the past year. Various aspects of the diagnosis, management, and pathophysiology of gout and gouty...
Article
To evaluate possible relationships between body size and articular architecture, femoral head radius and subchondral plate thickness were assessed in skeletal hip joints from normal primates. The relative "contact pressure" on bearing surfaces was estimated from the measured radius and the normal body mass in species ranging from Cebuella pygmaea (...
Article
The diagnosis of gout depends on showing urate crystals in synovial effusions or, with less certainty, recognizing a characteristic clinical presentation. The management of gout has four phases: control of inflammation, diagnostic evaluation, education of the patient, and treatment for the hyperuricemia. Sound logical principles guide each aspect....
Article
To determine whether the course of femoral head osteonecrosis after core decompression can be predicted from the extent of necrotic bone in the preoperative magnetic resonance imaging (MRI). In 31 femoral head lesions (Ficat stage I or II), the percentage volume of necrotic bone was calculated by dividing the sum of the necrotic areas from all MRI...
Article
Full-text available
Article
The search continues for constituents of articular cartilage in the serum and synovial fluid of patients with arthritis. This work is driven by the hope that such "markers" will be useful in the diagnosis and management of rheumatic diseases. Absent information about the kinetics of these molecules continues to hinder interpretation of their concen...
Article
Synovial perfusion was quantified in milliliters per minute per knee by two quite different clearance methods based on (1) counting tritiated water in serial aspirates of intraarticular saline, and (2) external counting of joints injected with free radioiodide. In each case, the serial counting data determine a rate constant that is multiplied by a...
Article
To examine the relative solubility of urate crystals in water, formalin, and ethanol. Weighed aliquots of synthetic crystals were incubated in each solvent for 72 h at 4 degrees C and were then examined by polarized microscopy. urate crystals were insoluble in alcohol, sparingly soluble in water, and markedly soluble in formalin. The marked solubil...
Article
By what mechanism do nonsteroidal anti-inflammatory drugs (NSAIDs) move from plasma into synovial fluid and back, and how does binding to plasma albumin in vitro relate to articular transport in vivo? To evaluate these issues, concurrent plasma and synovial fluid data of 8 different NSAIDs from 10 single-dose trials were analysed by a simple compar...
Article
Intra-articular injection of radiolabelled, commercial goat serum albumin (GSA) produces acute arthritis in caprine joints. This inflammation distorts clearance values and vitiates studies of normal lymphatic function. Endotoxin, routinely found in commercial albumin preparations, appears to cause this local reaction. We describe a simple method fo...
Article
Because the synovial lining is a major target organ of rheumatic diseases, it seems logical to seek understanding of those conditions through study of the normal and abnormal physiology of this specialized organ system. This brief review covers some basic principles and recent progress in this area with emphasis on our evolving knowledge of microva...
Article
The distal scapula and proximal humerus from each shoulder of nine adult dogs were slab-sectioned, cleaned of soft tissues, embedded in white plastic and stained black with a silver stain. These preparations were then photographed for automated, digital, morphometric analysis of subchondral bone structure. Comparison of transverse and coronal secti...
Article
Full-text available
Full textFull text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (271K), or click on a page image below to browse page by page. 957
Article
We measured articular blood flow by standard microsphere techniques in normal adult dogs at rest and during treadmill exercise. All animals but one underwent beta-adrenergic blockade as part of another experimental protocol. Expressed in microliter/min/g +/- SEM, baseline flow values to articular tissues were: knee synovium 26 +/- 4, femoral condyl...
Article
The clearance rates of free iodide and of radioiodinated serum albumin were measured in the knee and wrist joints of 9 normal adult dogs. Iodide clearance from the knee was 3 times greater than that from the wrist. In contrast, radioiodinated serum albumin clearance from the knee was only slightly greater than that from the wrist. Interpreted as re...
Article
Water moves between plasma (p) and synovial fluid (SF) in response to gradients in the balance of opposing hydrostatic pressures (HP) and oncotic pressures (OP). At the vascular site where proximal filtration ceases and distal reabsorption begins, all forces are theoretically in balance. At this point, the transitional microvascular pressure (TMP)...
Chapter
Two hydrodynamic findings have dominated recent research and clinical thinking on ischemic necrosis of bone, osteonecrosis. The first of these is an increased resting intraosseous pressure. This intraosseous hypertension is readily detected and has now been demonstrated in a variety of clinical settings. The finding is conceptually straightforward...
Article
In this report, we will review present knowledge of the concentrations of proteins in normal synovial fluid; we will consider the mechanisms that determine those concentrations; and we will suggest additional directions that still need to be pursued
Article
An 82-year-old man and a 34-year-old woman developed subacute, obstructive, fatal vasculopathies characterized by extensive crystalline tissue deposits and monoclonal lambda light chain serum components. Cryocrystalglobulinemia was also present in one patient, and the purified crystals contained only lambda light chain dimers. Although the presenta...
Article
For the most part, plasma concentrations of nonsteroidal antiinflammatory drugs (NSAID) have not correlated well with assessments of therapeutic response. This disappointing record may largely reflect weaknesses in experimental design. It may also be, however, that concentrations in plasma bear only a distant relationship to those in the inflamed t...
Article
In this issue of THE JOURNAL, Rosenthal et al1 report the case of an anephric, dialyzed patient experiencing acute arthritis associated with calcium oxalate crystals. Together with reports from Hoffman et al,2 Schumacher et al,3 and Reginato et al,4 this observation establishes an unequivocal place for oxalate among the solutes that abnormally crys...
Article
We measured intraosseous pressures in twenty human hips from cadavera during progressive serial applications of load using a materials-testing machine. Pressure rose in strict proportion to load at each of four different testing sites. In the femoral head, the mean response to loads applied over 0.1 second was 55 +/- 66 millimeters of mercury per 9...
Article
Ankylosing spondylitis patients who develop progressive spinal flexion may assume this posture to alleviate the pain of apophyseal arthritis. To examine this relationship, we scored injury to L4-L5 and L5-S1 apophyseal joints, as assessed by computed tomography, in 10 men with early ankylosing spondylitis. Both by the modified Schober test and by r...
Article
This study introduces hydraulic resistance (HR) as a new method to measure intraosseous vascular outflow resistance in the human proximal femur. HR is the standard measure of resistance to fluid flow in porous matrices and is derived from serial pressure/flow determinations. Eighteen hips were studied in 11 patients taken to surgery for core decomp...
Article
Flat foot, a major cause of foot pain and disability, may result from rupture of the tibialis posterior tendon. We describe 2 patients with rheumatoid arthritis who developed flat feet secondary to surgically confirmed tendon rupture, and we discuss the anatomy and diagnosis of this condition. In the second patient, we also present the results of t...
Article
Concentrations of 5 marker proteins were measured in synovial fluid and serum samples from knee effusions of 11 patients with rheumatoid arthritis and 9 with osteoarthritis. Indirect determinations of synovial plasma flow and lymphatic drainage were obtained by measuring iodide clearance (ml/minute) and radio-albumin clearance (ml/minute). Together...
Article
Both the rate and the efficiency of uric acid excretion were evaluated in a 28 year old gouty woman and in 16 additional members of her family. Mid-morning, spot blood and urine specimens were obtained from three generations of the kindred, living in Washington, Montana, British Columbia and Alaska. The excretion rate of uric acid, calculated per d...
Article
Published data both support and dispute the existence of urate binding to serum proteins. The issue remains important since such binding could be relevant to both renal transport and tissue deposition of urate. Using equilibrium dialysis over 18 hours, we studied the effects of selected cations on 14C-urate binding to human albumin (5 g/dl) in TRIS...
Article
Iodide clearance was measured in the chronic knee effusions of 11 patients with rheumatoid arthritis and 9 patients with osteoarthritis. The mean (±SE) iodide clearance of 1.92 ± 0.30 ml/minute in rheumatoid arthritis effusions did not differ significantly from the 2.19 ± 0.52 ml/minute found in osteoarthritis effusions. Clearance values in rheumat...
Article
Apparent crystal-negative effusions are sometimes seen in the early course of acute gouty arthritis. Also, newly-prepared urate crystals become less phlogistic after heating in vitro. A plausible explanation for these phenomena lies in the tendency for some solutes to precipitate first as unstable hydrated crystals which then evolve into more stabl...
Article
Intraarticular volumes were measured by radiolabeled albumin (RISA) distribution in chronic knee effusions from 11 rheumatoid arthritis patients and 9 osteoarthritis patients. Volumes of synovial fluid obtained at joint aspiration were substantially less than those found by RISA dilution. Up to 24 hours was needed for full distribution of RISA thro...
Article
The hydraulic properties of trabecular bone were explored in both sides of normal canine shoulders by following the hydrostatic pressure response to transchondral injections of saline. In a series of isovolumetric injections at sites 9 mm beneath either joint surface, the pressure consistently rose higher and lasted longer in the humerus than it di...
Article
Humeral and scapular components of normal canine shoulders were used to load each other in a special testing jig permitting measurement of subchondral plate deflection on each side of the joint. In eleven shoulders, at three loading rates, the humeral compliance (mu deflection kg load-1) was always greater than that of the glenoid fossa (geometric...
Article
The medical management of gout follows a logical course in eventually controlling the underlying hyperuricemia. Approached properly, it is one of the most gratifying rheumatic diseases for a physician to treat.
Article
The colloid osmotic pressure of synovial fluid from canine shoulders, elbows, wrists, hips, and knees varied significantly from one joint to the next with the lowest values regularly present in wrists. These differences imply a corresponding, regular variation in microvascular function which may contribute to the distribution patterns of specific r...
Article
Antirheumatic drug concentrations have been measured in human synovial fluid and synovial tissue, and provide insights on: (1) extravascular pharmacokinetics; (2) articular pathophysiology; and (3) the factors which modify drug levels in inflamed tissues. Concentrations of free drug in synovial fluid and plasma are the same in all conditions except...
Article
For the immediate future, it appears likely that tendinitis and bursitis of the shoulder will continue to be important clinical and epidemiologic concerns, especially for older working people, who are most vulnerable to these problems. Aggressive local and systemic therapy now seem capable of controlling symptoms in the great majority of affected p...
Article
Highly significnt correlations have been demonstrated between gout and degenerative disease of the tarsal joint and the knees. Degenerative changes are not likely to cause sufficient differences of temperature or pH to explain the selective precipitation of urate crystals in and about the first metatarsophalangeal joint. More logical reasons for th...

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Project
This proposed editorial is intended to explain the tidemark as a deposit of chondrocytic debris, to explain the mechanism of its sometimes duplication, and to suggest its potential role as a source of antigens in the pathophysiology of rheumatoid arthritis.