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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

Gout and hyperuricemia.

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 arthritis have been recently reviewed. The therapy of gout and hyperuricemia continue to lead to significant complications.

Crystallization

Zinc, again.

Explore the source record for details and available documents.

Adrenal Cortex Hormones

Subchondral plate thickness reflects tensile stress in the primate acetabulum.

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 (0.1 kg) to Gorilla gorilla (170 kg). Subchondral plate thickness was evaluated by computed tomography in species ranging from Cercopithecus neglectus (4.0 kg) to Gorilla gorilla. Neither the "contact pressure" nor the thickness of the femoral subchondral plate varied substantially among species. In contrast, the acetabular subchondral plate thickened significantly (p = 0.01) as body size increased. This finding is interpreted as an osseous response to tensile acetabular stress, which can be expected to increase directly with the radius of curvature.

Acetabulum

Synovial perfusion in the human knee: a methodologic analysis.

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 distribution volume to provide the clearance in flow terms of milliliters per minute. This report updates and summarizes these data and compares the two methods to each other and to alternative assessments of synovial blood flow. Available methods such as laser Doppler flowmetry (with data output measured in volts) and solute clearance constant determinations (in min-1) are useful for selected purposes but cannot be used to quantify the articular flux (in milligrams per minute) of any solute. Radiolabeled microspheres provide data (in milliliters per minute per g of tissue) but are unsuitable for human use. The two clearance methods provide comparable results, but the free iodide technique seems most suitable for physiologic investigations. The latter potentially includes critical evaluations of synovial blood flow in relation to issues such as palpable warmth, visible erythema, articular ischemia, the permeability of synovial vessels, the genesis of effusions, the delivery and removal of therapeutic agents, and the concentration of every synovial fluid solute from micronutrients through cytokines, plasma proteins, and molecular markers of cartilagenous injury.

Adult

Cartilage matrix molecules in serum and synovial fluid.

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 concentration. Recent progress includes recognition of markers that appear to be specific for diseased cartilage and identification of factors that may distinguish between reversible and irreversible disease.

Cartilage

Quantitative magnetic resonance imaging predicts clinical outcome of core decompression for osteonecrosis of the femoral head.

OBJECTIVE: 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). METHODS: 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 slices by the sum of the femoral head areas. Osteonecrosis risk factors, pain scores, and the need for further surgery were assessed at a minimum of 12 mo post-core decompression. Clinical outcomes were considered good when post-core decompression pain scores improved and further surgery was not required. RESULTS: Fourteen of the 15 hips with good outcomes after a mean followup of 32 mo had less than 21% femoral head involvement. All 16 hips with poor outcomes after a mean followup of 17 mo had more than 21% of the femoral head affected. CONCLUSION: Quantitative MRI of femoral head necrosis was a useful predictor of clinical outcome following core decompression.

Adult

Not water, but formalin, dissolves urate crystals in tophaceous tissue samples.

OBJECTIVE: To examine the relative solubility of urate crystals in water, formalin, and ethanol. METHODS: Weighed aliquots of synthetic crystals were incubated in each solvent for 72 h at 4 degrees C and were then examined by polarized microscopy. RESULTS: urate crystals were insoluble in alcohol, sparingly soluble in water, and markedly soluble in formalin. CONCLUSION: The marked solubility of urate in formalin is consistent with formation of urate:formaldehyde addition products.

Crystallization

Articular pharmacokinetics of protein-bound antirheumatic agents.

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 compartmental model incorporating intra-articular volume, synovial plasma flow rates and protein transport. All pharmacological and physiological data were taken from published studies of chronic knee effusions in patients with rheumatoid arthritis. The analysis shows that these protein-bound NSAIDs readily leave the vasculature and enter synovial fluid during each transit of synovial microvessels. The mean rate of transport, 0.23 min-1, is consistent with passive diffusion at rates far in excess of those attributable to movement of albumin-bound drug or of the small, free-drug fraction found by equilibrium dialysis. These findings are explained by association and dissociation of NSAIDs and albumin that occur far more rapidly than vascular transit. Ongoing dissociation makes bound drug available for transvascular exchange and thereby diminishes the pharmacokinetic significance of binding data obtained in vitro.

Anti-Inflammatory Agents, Non-Steroidal

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