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Biomedical subjects

P A Simkin

Publications and source records attributed to P A Simkin.

At least 19 recordsLinked to original sources
PubMed1992

Avoidance of endotoxin-induced inflammation during studies of albumin clearance from caprine joints.

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 for the preparation of low-endotoxin, radioiodinated serum albumin from aseptically collected serum. We have used this technique to prepare GSA for use as a tracer molecule in clearance studies of synovial joint lymphatic function. The isolated protein exhibits antigenic and chemical characteristics indistinguishable from those of commercial GSA but contains at least 1000-fold less endotoxin. In contrast to commercial GSA preparations, this albumin does not produce local inflammation when injected into synovial joints and is cleared from caprine joints in the normal monoexponential manner. Low levels of endotoxin seriously distort studies of articular albumin kinetics and may induce comparable artifacts when commercial protein preparations are used to study other physiological systems.

Animals↗
PubMed1991

Physiology of normal and abnormal synovium.

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 microvascular function.

Animals↗
PubMed1991

Subchondral architecture in bones of the canine shoulder.

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 sections through the left and right shoulders demonstrated essential isometry of trabecular patterns within each bone. Comparison of the scapula and humerus revealed significant differences in bony architecture. The subchondral plate was an average of 5.6 times thicker under the glenoid fossa than in the opposing humeral head. Deeper trabecular structure also differed with the trabecular bone volume (density) in the humerus being greater than that in the scapula. This difference reflects a greater trabecular density in the humerus with comparable trabecular thickness in both bones. These structural differences are consistent with previous functional studies of the same two bones that revealed greater mechanical stiffness beneath the glenoid fossa and greater hydraulic resistance within the humeral head.

Animals↗
PubMed1990

Iodide and albumin kinetics in normal canine wrists and knees.

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 respective indices of effective synovial plasma flow and lymphatic drainage, these values indicate that the filtration fraction is normally greater in microvessels of the wrist than in those of the knee. These findings complement the results of companion studies of Starling forces that indicate a higher pressure microvascular bed in the wrist than in the knee.

Animals↗
PubMed1990

Hydrostatic and oncotic determinants of microvascular fluid balance in normal canine joints.

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) may be estimated from the equation TMP = HPSF + OPP - OPSF. We measured these forces in the shoulders, wrists, and knees of 10 normal dogs, ages 2-10 years. The mean HPSF in the knee was lower than that in the shoulders and significantly lower than that in the wrist. Conversely, the OPSF in the wrist was significantly lower than that in the shoulder or the knee. These factors combined indicate that the microvascular bed in the normal knee has a remarkably low mean TMP (7.9 mm Hg). We also found a strong positive correlation between the age of each dog and the mean oncotic pressure of its SF.

Animals↗
PubMed1990

Effects of exercise on blood flow to canine articular tissues.

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 condyle 130 +/- 21, tibial plateau 182 +/- 29, articular fat pad 9 +/- 2, knee ligaments 17 +/- 3, menisci 34 +/- 6, wrist synovium 19 +/- 4, distal radius 65 +/- 13, and lunate bone 59 +/- 13. Blood flow increased with exercise in all soft tissues of both the knee (stifle joint) and the wrist (radiocarpal joint). Geometric mean exercise/rest flow ratios ranged from a low of 1.44 (p less than 0.05) in the menisci of the knee to a high of 7.25 (p less than 0.001) in the synovium of the wrist. In contrast, blood flow did not rise in juxtaarticular bones and fell significantly in femoral condyles (mean flow ration 0.71, p less than 0.005). These findings indicate that articular soft tissues derive increased perfusion from the redistribution of blood flow that accompanies short-term exercise. In contrast, flow to juxtaarticular bone does not increase under these conditions.

Adrenergic beta-Antagonists↗
PubMed1989

A vasculopathy with deposition of lambda light chain crystals.

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 presentation of these patients resembled that of systemic necrotizing vasculitis, histologic evidence of inflammation was lacking and their subsequent rapid clinical deterioration was not altered by corticosteroid therapy, and in one case cyclophosphamide and plasmapheresis. Both patients died within 3 weeks of presentation.

Adult↗
PubMed1988

Tibialis posterior tendon rupture: a cause of rheumatoid flat foot.

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 tendon imaging with both magnetic resonance and ultrasound.

Aged↗
PubMed1988

Apophyseal arthritis limits lumbar motion in patients with ankylosing spondylitis.

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 radiography of the lateral spine, impaired spinal motion correlated highly with evidence of apophyseal injury.

Adolescent↗
PubMed1988

Hydraulic resistance: a measure of vascular outflow obstruction in osteonecrosis.

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 decompression therapy of presumable atraumatic osteonecrosis of the femoral head. HR was much higher in osteonecrotic (174 +/- 29 mm Hg min/ml, SE) than in normal human cadaveric femora (14 +/- 6) and was also higher in subcapital (253 +/- 39) than intertrochanteric sites (78 +/- 17). HR correlated highly with baseline intraosseous pressure (r = 0.74, p less than 0.001). HR testing is a simple, practical method which quantifies outflow obstruction of the intraosseous circulation. We believe this test will be helpful in the diagnosis of atraumatic osteonecrosis and in the understanding of its underlying pathophysiology.

Adult↗
PubMed1988

Concentration-effect relationships of NSAID.

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 tissues where NSAID presumably act. Elimination kinetics, protein binding, fat solubility, tissue blood flow, and uptake by cells may be determinants of concentration and response in target tissues. These factors are considered as they relate to NSAID concentrations in synovial effusions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

The effect of compressive loading on intraosseous pressure in the femoral head in vitro.

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 980 newtons. This value was 3.6 times higher than the mean response in a region cephalad to the acetabulum and 2.6 and 2.8 times higher than the mean response in the femoral neck and intertrochanteric regions. In further studies within the femoral head, pressures were accentuated and reduced by factors of 1.7 and 0.4, respectively, at faster (0.03 second) and slower (1.0 second) loading times.

Biomechanical Phenomena↗
PubMed1987

Protein traffic in human synovial effusions.

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 with protein concentrations, these determinations allowed us to calculate: the flux of each marker protein through synovial tissues (mg/minute); the volume of plasma cleared by synovium per unit time (ml/minute); and the fractional extraction per passage through the synovial microcirculation (protein permeance). These measures differed substantially between rheumatoid arthritis and osteoarthritis patient populations and quantified the severity of the microvascular lesion in rheumatoid synovitis.

Arthritis, Rheumatoid↗