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Biomedical subjects

D P Page-Thomas

Publications and source records attributed to D P Page-Thomas.

12 recordsLinked to original sources
PubMed1992

The use of a chelating derivative of alpha melanocyte stimulating hormone for the clinical imaging of malignant melanoma.

A novel chelating derivative of alpha melanocyte stimulating hormone, bis MSH-DTPA, has been used for the diagnostic targeting of malignant melanoma. 15 patients were investigated of whom nine were shown by other means to have active disease at the time of the scan. Tumours were imaged in all of these nine patients. Of a total of 46 lesions over 10 mm encountered, 41 (89%) were imaged. There were no false positives and in two cases bisMSH-DTPA was instrumental in reversing diagnoses made using ultrasound. Derivatives of melanocyte stimulating hormone may be of considerable value in targeting melanomas.

Adult↗
PubMed1990

A chelating derivative of alpha-melanocyte stimulating hormone as a potential imaging agent for malignant melanoma.

A chelating derivative of alpha-melanocyte stimulating hormone (MSH) has been synthesised, in which two molecules of the hormone are cross-linked by diethylenetriamine pentaacetic acid (DTPA). This compound, bisMSH-DTPA, was equipotent with MSH in an in vitro tyrosinase assay with Cloudman S91 melanoma cells. When DBA/2 mice bearing the same tumour were injected with bisMSH-DTPA labelled with the gamma-emitting isotope indium-111 (111In), the radioactivity became rapidly associated with the melanoma tissue. By 24 h post-injection, radioactivity in tumour tissue was significantly higher (P less than 0.001) than in spleen, lung, brain, eye and skin. Uptake of radioactivity by the tumours was inhibited by a 200-fold molar excess of MSH, whereas uptake by liver, kidney, spleen, lung, brain, eye and skin was unaffected. We conclude that bisMSH-DTPA may offer an alternative to antibody targeting in the imaging of malignant melanoma.

Animals↗
PubMed1989

Factors influencing pertechnetate uptake by rabbit knees.

The accumulation of radioactivity over rabbit knees immediately after the injection of 99mTc-pertechnetate or one of two 99mTc-labelled particulate preparations has been measured in animals with and without experimental arthritis. The results indicate that in inflamed, but not normal joints, a peak of radioactivity is detectable within 9 seconds of injection and suggest that the rate of accumulation of radioactivity over the joint may be a more sensitive indicator of inflammatory activity than measurement at a fixed time. Clearance from the circulation and tissue distribution of the three radioactive preparations were also measured.

Animals↗
PubMed1987

Clearance of proteoglycan from joint cavities.

The rate of loss from the synovial cavity of proteoglycan subunit, a major constituent of cartilage, has been measured in rabbits with and without experimental arthritis. The effect of aggregation between proteoglycan and hyaluronic acid upon the rate of elimination has also been investigated. The results indicate that proteoglycan subunit has a clearance half life of around 12 hours in normal joints and that this rate is not significantly altered in the presence of an active synovitis. Neither injection of proteoglycan as an aggregate, nor in a form incapable of aggregation, had any significant effect on clearance rates. These data indicate that loss of proteoglycan from the joint is not retarded by its ability to aggregate with hyaluronic acid in the synovial fluid and, together with measurements of synovial fluid proteoglycan, may enable rates of cartilage breakdown in vivo to be calculated.

Animals↗
PubMed1984

Thermologic methods in clinical pharmacology-skin temperature measurement in drug trials.

With the increasing availability of thermographic equipment the definition of "thermography" and "thermologic methods" is important, since differing techniques and standards may be applied. Recommendations are given for optimum use of skin-surface temperature measurements in the assessment of clinical drug trials. Sites for thermographic measurement, different methods for quantitation, and sources of further information are included. A brief checklist of minimal technical requirements and an example of information for patients are also included.

Drug Evaluation↗
PubMed1983

Heat distribution over normal and abnormal joints: thermal pattern and quantification.

We have identified regular thermal patterns over normal knee, ankle, and elbow joints and demonstrate how synovitis affecting these joints may be identified by alteration or loss of the thermal pattern. Sixty healthy volunteers were thermographed on a total of 190 occasions, and 614 out of 618 joints conformed to the normal thermal pattern. Eighty-five patients with synovitis of at least one of the specified joints were thermographed on a total of 339 occasions, and 322 out of 1362 thermograms were abnormal. No joint with clinical evidence of synovitis had a normal thermal pattern. As temperature-based parameters have been found to show marked diurnal variation and relative frequency distributions do not have this drawback, we suggest that quantification of synovitis by thermography should in future be based on abnormalities of thermal pattern rather than absolute skin temperature values.

Adolescent↗
PubMed1981

The production in culture of metalloproteinases and an inhibitor by joint tissues from normal rabbits, and from rabbits with a model arthritis. I. Synovium.

During 5 days of culture, explants of normal rabbit synovium produced no active collagenase, negligible latent collagenase, but significant levels of free collagenase inhibitor. Synovium from joints exhibiting a proliferative arthritis produced greatly elevated levels of collagenase; the appearance of active enzyme in the medium during the second day of culture was associated with the disappearance of free inhibitor. Enzyme levels in the media correlated well with the arthritic status of joints, when explants were prepared up to 10 weeks after the induction of the model arthritis. Synovium from the contralateral joints of rabbits with unilaterally induced arthritis produced no active collagenase, but approximately one-third as much latent collagenase as found with arthritic joints. Enzymatic activities against gelatin and cartilage proteoglycan substrates were demonstrated in synovial culture media in addition to collagenolytic activity. Gel filtration showed that these activities were not due to a single enzyme, and further characterisation confirmed that the enzymes were metalloproteinases. The results are considered in the light of published data, and the involvement of metalloproteinases and their specific inhibitor in the development of arthritic lesions is discussed.

Animals↗
PubMed1981

The production in culture of metalloproteinases and an inhibitor by joint tissues from normal rabbits, and from rabbits with a model arthritis. II. Articular cartilage.

During the development of proliferative arthritis in the knee joints of rabbits, there was a large increase in the ability of articular cartilage explants to produce latent collagenase in culture. In parallel, the normally high levels of collagenase inhibitor produced by cartilage in culture fell, but active collagenase was never detectable. Characterisation of the collagenase and other proteinase activities produced by rabbit articular cartilage in culture showed that two activities could be separated by gel filtration, one with activities on gelatin and cartilage proteoglycan and the other degrading collage. Under the conditions employed in this paper no resolution of the gelatin and proteoglycan activities could be achieved. All the activities were in a latent form, activated by 4-aminophenylmercuric acetate (APMA), and inhibited by 1,10-phenanthroline or EDTA, but not by di-isopropylfluorophosphate (DFP), indicating that they are metalloproteinases. Characterization of the collagenase inhibitor showed a single peak of activity of apparent molecular weight of 28,000 on gel filtration. The inhibitor was sensitive to APMA and also inhibited other rabbit metalloproteinases, analogous to the system described for rabbit bone. The physiological significance of the synthesis by articular cartilage of proteinases that destroy connective tissue macromolecules and the presence of an enzyme-inhibitor control system is discussed.

Animals↗
PubMed1979

Monitoring of experimental arthritis in rabbits.

The effect of ambient temperature and air flow on the radiometric measurement of experimental arthritis in rabbit knee joints has been studied. Temperature changes due to inflammation in such joints could be detected up to 70 days after induction of the arthritis by the use of radiometry. The method has been used to quantitate the anti-inflammatory activity of intra-articularly injected cortisol acetate and orally administered aspirin. It is suggested that this method of noninvasive monitoring has a number of advantages over other procedures.

Animals↗
PubMedDate not supplied

Effect of the intra-articular injection of lutetium-177 in chelator liposomes on the progress of an experimental arthritis in rabbits.

The treatment of rheumatoid arthritis by radiosynovectomy has been restricted by the difficulty of preventing leakage of the radioisotope from the joint cavity. We have previously shown that this leakage can be reduced to very low levels by delivering the radioisotope in liposomes containing the lipophilic chelator, 3-cholesteryl 6-[N'-iminobis-(ethylenenitrilo)tetraacetic acid]hexyl ether. The present study investigates the effectiveness of the beta-emitting isotope lutetium-177, delivered in chelator liposomes, in treating an experimental arthritis in rabbits. Chelator liposomes containing 0.35 mCi, 0.175 mCi Or 0.087 mCi of the isotope were injected into the synovial cavities of the knees of rabbits with an established experimental arthritis. The retention of the lutetium and the progress of the arthritis were followed for 47 days, and samples of the joint tissues were taken for histology at the end of the experiment. Results showed that losses of radioactivity averaged less than 1% per day over 47 days and that joints treated with 0.175 mCi showed significant reductions in both diameter and surface temperature compared with controls treated with a non-radioactive preparation. Post-mortem histology revealed that, whereas control joints showed a highly active synovitis, synovia of joints treated with 0.175 or 0.35 mCi lutetium-177 had very little inflammatory activity. Although some joints which had received 0.35 mCi showed signs of damage to the articular cartilage, this damage was not apparent wih either of the two lower doses. We conclude that, in this animal model, chelator liposomes complexed with a suitable radioisotope are capable of effecting an efficient synovectomy.

Animals↗