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Biomedical subjects

S Shortkroff

Publications and source records attributed to S Shortkroff.

At least 37 records · Page 2Linked to original sources
PubMed1993

Enhancement of joint fluid with intravenously administered gadopentetate dimeglumine: technique, rationale, and implications.

This study reports findings on joint fluid enhancement after intravenous administration of gadopentetate dimeglumine. Ten subjects were studied: two asymptomatic volunteers and eight patients with suspected meniscal tears. The subjects underwent imaging at 1.5 T before, immediately after, and 42-60 minutes after intravenous administration of gadopentetate dimeglumine. The rate of fluid enhancement was assessed in three subjects, and the effects of exercise were studied. All subjects exhibited enhancement of joint fluid. Mean fluid enhancement for patients was 137% on initial and 262% on delayed images obtained after exercise. Exercise increased the rate and degree of fluid enhancement and distributed contrast material uniformly throughout the joint. The arthrographic effect of the fluid enhancement increased the number of perceived cartilage defects. This study documents enhancement of joint fluid in healthy subjects and in those with effusions. The arthrographic effect may provide a more convenient alternative to intraarticular injection of gadopentetate dimeglumine for MR arthrography.

Contrast Media↗
PubMed1992

Synovium-like tissue from loose joint replacement prosthesis: comparison of human material with a canine model.

The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-1), prostaglandin E2 (PGE2), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision arthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte proliferation assay to determine IL-1-like activity. IL-1 beta levels in human cell-conditioned media were analyzed by enzyme-linked immunosorbent assay, and PGE2 levels were measured by radioimmunoassay (RIA) using a PGE2 RIA kit (New England Nuclear). Human tissue contained levels of IL-1 beta in the range of 150 to 7,040 pg/mL and PGE2 levels of 82 to 952 ng/mL. The canine specimens contained IL-1-like activity and significant amounts of PGE2 (76 to 1,720 ng/mL). Naproxen decreased PGE2 levels in vitro. This animal model provides the means to investigate the in vivo and in vitro activity of the synovial cells around loose total joint prostheses.

Adult↗
PubMed1990

Effects of isolated rheumatoid synovial cells on cartilage degradation in vitro.

Rheumatoid synovium in coculture with cartilage has been shown to release a factor(s) that stimulates the depletion of glycosaminoglycans (GAG) from cartilage matrix. Human rheumatoid synovium was enzymatically disaggregated and the isolated cells were subjected to a variety of mechanical and immunological treatments. Synovial cell conditioned media (SCCM) were prepared and analyzed for their ability to stimulate GAG depletion. SCCM prepared from increasing concentrations of isolated synovial cells demonstrated cartilage degradative activity in a dose-dependent manner. This activity was characterized as interleukin-1 like and was found mostly within the adherent cell population where the synovial macrophages retained significant degradative ability. T cells alone were found to have no direct degradative effect on cartilage, but their presence appeared to augment the response of the adherent cells. The techniques described here provide a quantitative model for examining the degradative factors from synovium as well as the cellular interactions that promote their release.

Animals↗
PubMed1990

Rhenium heptasulfide: a potential carrier system for radiation synovectomy.

Rhenium sulfide colloid was prepared by the thiosulfate acid reduction method and assessed for its applicability as a particle carrier for use in radiation synovectomy. In vitro stability studies demonstrated that greater than 95% of the 186Re activity remained in colloidal form over a 5 day period. Intraarticular knee injections of 186Re2S7 into normal and arthritic rabbit joints were followed by gamma camera imaging and by biodistribution in order to quantify the leakage to different organs. Mean retentions of 186Re in knees, determined by gamma camera imaging were 97(+/- 4)%, 92(+/- 7)%, 89(+/- 9)% and 88(+/- 10)% at 1 h, 1, 2 and 3 days, respectively. The percent injected dose was 0.0023% in the lymph nodes, 1.65% in the liver, 0.006% to the spleen, 0.013% in the lungs, 0.35% in the kidney, 0.014% in the heart, 0.12% in the bone, 0.7% in the muscle, 0.3% in the fat and 0.6% in the blood.

Animals↗
PubMed1990

Biochemical and histological evaluation of the synovial-like tissue around failed (loose) total joint replacement prostheses in human subjects and a canine model.

The tissue around loose total joint replacement prostheses displays a synovial-like lining comprised of cells that produce IL-1 and PGE2, mediators of inflammation that stimulate bone resorption. Particles of titanium alloy, as well as cobalt-chromium alloy and polyethylene, were found to aggravate the histiocytic response and production of IL-1 and PGE2. Tissue with similar histological and biochemical features was produced in a canine model of the aseptic loose cemented femoral stem.

Animals↗
PubMed1990

Tissue changes around loose prostheses. A canine model to investigate the effects of an antiinflammatory agent.

The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process.

Animals↗
PubMed1989

Treatment of antigen-induced arthritis in rabbits with dysprosium-165-ferric hydroxide macroaggregates.

Dysprosium-165-ferric hydroxide macroaggregates (165Dy-FHMA) was used as an agent of radiation synovectomy in an antigen-induced arthritis model in New Zealand white rabbits. Animals were killed up to 6 months after treatment. 165Dy-FHMA was found to have a potent but temporary antiinflammatory effect on synovium for up to 3 months after treatment. Treated knees also showed significant preservation of articular cartilage architecture and proteoglycan content compared with untreated controls, but only during the first 3 months after treatment. In animals killed 3 and 6 months after treatment there were only minimal differences between the treated and untreated knees, indicating that the antiinflammatory effects on synovial tissue and articular cartilage preservation were not sustained.

Animals↗
PubMed1988

Repeat radiation synovectomy with dysprosium 165-ferric hydroxide macroaggregates in rheumatoid knees unresponsive to initial injection.

Because of failure to fully respond to an initial intraarticular injection of dysprosium 165-ferric hydroxide macroaggregates, 17 patients with seropositive rheumatoid arthritis underwent repeat radiation synovectomy using this agent. Of the 13 patients who were evaluated 1 year later, 54% (7 knees) had good results, 31% (4 knees) had fair results, and 15% (2 knees) had poor results. The initial lack of significant benefit from radiation synovectomy did not appear to preclude a favorable response to a second injection.

Adult↗
PubMed1988

Use of liposomes as carriers for radiation synovectomy.

Using [99mTc]pertechnetate as an aqueous space marker, the permeability of liposomes composed of seven different mixtures of distearoylphosphatidylcholine (DSPC) and sphingomyelin (SM) was determined. Liposomes containing 20-33% SM were the least permeable in the presence of rheumatoid synovial fluid. Following injection of 99mTc-containing liposomes into the knee joints of rabbits, retention of 99mTc in the knee was more than 200 times greater than following injection of nonencapsulated [99mTc]pertechnetate. The knee clearance biologic half time of 99mTc with DSPC/SM (4:1) liposomes was 64 h. Most of the activity that had leaked from the knee was not found in extra-articular tissues, suggesting rapid excretion. When DSPC/SM (4:1) liposomes were labeled with 111In(oxine), a knee clearance biologic half time of greater than 1200 h was observed.

Animals↗
PubMed1987

Experimental arthritis induced by polysaccharide macromolecules.

Several polysaccharide macromolecules are capable of inducing synovial inflammation. Characteristics of polysaccharides that have this capacity were studied in an in vivo rabbit model. The ability to induce synovial inflammation was positively correlated with the presence of sulfate and with high molecular weight. Understanding the characteristics of molecules that produce inflammation may help in the investigation to determine what mechanisms initiate the inflammatory response.

Animals↗
PubMed1987

Treatment of rheumatoid arthritis using radiopharmaceuticals.

One hundred and twenty one knees in 97 patients with seropositive rheumatoid arthritis and persistent knee synovitis were treated with the intra-articular injection of 270 mCi (30 GBq) of dysprosium-165 (165Dy) bound to ferric hydroxide macroaggregates. Of 81 knees evaluated at one year, 61% had good results, 23% had fair results and 16% had poor results. Of 44 knees evaluated at two years, 64% had good results, 16% had fair results and 20% had poor results. Knees with Stage I radiographic changes showed 72 and 81% good results at one and two years, respectively. Knees and Stage II radiographic changes showed 53 and 48% good results at one and two years, respectively. Leakage of radioactivity from the injected joint was minimal. Mean leakage to the venous blood was 0.15% of the injected dose. Mean leakage to the liver 24 h after injection was 0.64% of the injected dose. Mean leakage to the draining inguinal lymph nodes was 0.17% of the injected dose. These results indicate that 165Dy-ferric hydroxide macroaggregate is an effective agent for radiation synovectomy, particularly in knees with Stage I radiographic changes. The minimal leakage rates observed offer a definite advantage over previously used agents.

Adult↗
PubMed1987

Evaluation of indium-111 chloride as a radiopharmaceutical for joint imaging in a rabbit model of arthritis.

The potential use of 111In-chloride as a radiopharmaceutical for quantitating the extent of synovitis was investigated in a rabbit model of antigen-induced arthritis. Rabbits with monoarticular disease were injected with 111In-chloride and imaged at 30 minutes and 24, 48, 72, and 96 hours. In control knee joints, the ratio of activity in the knee to a soft-tissue region in the thigh remained constant (1.5-1.85:1); in arthritic knees, the 111In uptake ratio increased from 2:1 to 3.2, 3.5, 3.9, and 4.6:1 at the later time points. The difference between the knee-to-soft-tissue ratios observed in the control and involved joints was significant (P less than .01, 48-96 hr). Tissue distribution measurements demonstrated that the synovium and intra-articular structures covered by synovium in arthritic joints had the highest concentration of 111In. In control joints, these tissues were found to take up tenfold less activity. Good correlation was observed between the 111In knee-to-soft-tissue ratios calculated from the images and histologic assessment of the severity of synovitis.

Animals↗
PubMed1987

Synovectomy of the rheumatoid knee using intra-articular injection of dysprosium-165-ferric hydroxide macroaggregates.

One hundred and eleven patients who had seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with intra-articular injection of 270 millicuries of dysprosium-165 bound to ferric hydroxide macroaggregates. A two-year follow-up was available for fifty-nine of the treated knees. Thirty-nine had a good result; nine, a fair result; and eleven, a poor result. Of the twenty-five knees that had Stage-I radiographic changes, nineteen had a good result. Of the thirty-four knees that had Stage-II radiographic changes, twenty showed a good result. Systemic spread of the radioactivity from the injected joint was minimum. The mean whole-body dose was calculated to be 0.3 rad and that to the liver twenty-four hours after injection, 3.2 rads. The results indicated that dysprosium-165-ferric hydroxide macroaggregate is an effective agent for performing radiation synovectomy, particularly in knees that have Stage-I radiographic changes. Because of the minimum rate of systemic spread of the dysprosium-165, it offers a definite advantage over agents that previously have been used.

Adult↗
PubMed1986

Treatment of rheumatoid synovitis of the knee with intraarticular injection of dysprosium 165-ferric hydroxide macroaggregates.

One hundred eight knees of 93 patients with seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with an intraarticular injection of 270 mCi of dysprosium 165 bound to ferric hydroxide macroaggregate. Leakage of radioactivity from the injected joint was minimal. Mean leakage to the venous blood 3 hours after injection was 0.11% of the injected dose; this corresponds to a mean whole body dose of 0.2 rads. Mean leakage to the liver 24 hours after injection was 0.64% of the injected dose; this corresponds to a mean liver dose of 3.2 rads. In 7 additional patients examined, there was negligible or near negligible activity found in the draining inguinal lymph nodes. One-year followup was possible for 74 knees (63 patients). Sixty-one percent of the knees had good results, 23% had fair results, and 16% had poor results. There was a direct correlation between the radiographic stage and response to treatment. In knees with stage I radiographic changes, 72% showed good results; 93% showed improvement. In knees with stage II changes, 59% showed good results; 81% showed improvement. These preliminary results indicate that dysprosium 165-ferric hydroxide macroaggregate is an effective agent for radiation synovectomy. The low leakage rates observed offer a definite advantage over agents previously used.

Adult↗
PubMed1986

Radiation synovectomy with 165Dy-FHMA: lymph node uptake and radiation dosimetry calculations.

The lymph node uptake of 165Dy was measured in 25 patients treated by radiation synovectomy via intra-articular injection of 165Dy-ferric hydroxide macroaggregates (FHMA). An average of 0.12% of the injected dose was found in the inguinal lymph nodes 19h post injection. This results in a lymph node of 16.6 rad (166 mGy), a dose significantly less than that reported following radiation synovectomy with other radiocolloids. Dosimetry calculations for the intra-articular injection of 165Dy-FHMA are provided in the appendix.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Experimental radiation synovectomy by 165Dy ferric hydroxide macroaggregate.

The short half-life beta emitter 165Dy coprecipitated as a macroaggregate with ferric hydroxide (FHMA) has been shown to destroy knee synovium in the antigen-induced arthritic rabbit. Using 153Gd as a gamma tracer for leakage studies revealed that the leakage of this system from rabbit knee joints never exceeded 1.2% over 24 hours. This is such less than the leakage rates reported from any human studies or our rabbit studies using 198Au.

Animals↗