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Biomedical subjects

M Frier

Publications and source records attributed to M Frier.

34 records · Page 2Linked to original sources

Monoclonal antigranulocyte antibody imaging in inflammatory bowel disease: a preliminary report.

The 99Tcm-labelled antigranulocyte antibody BW250/183 has been used in the detection of intestinal inflammation in patients with active ulcerative colitis and Crohn's disease. Planar images were obtained up to 24 h after intravenous injection of the antibody. Eight out of nine patients with ulcerative colitis and six out of seven patients with Crohn's disease gave positive images. In 11 patients distribution of the inflammation was confirmed by barium studies, colonoscopy or surgery, whilst in two the antibody scan suggested more extensive disease than barium enema. None of the patients had any adverse reactions. Imaging with BW250/183 appears to give an accurate indication of the extent of inflammation in inflammatory bowel disease.

Colitis, Ulcerative

Double-blind randomized trial of perioperative fibrinolytic enhancement for femoropopliteal bypass.

Patients with rest pain or acute peripheral arterial thrombosis are known to have impaired endogenous fibrinolysis, which is associated with an increased risk of early vascular graft thrombosis. This risk is exacerbated by the fibrinolytic shutdown which is known to occur after major surgery. Stanozolol, which has been demonstrated to enhance endogenous fibrinolysis, was therefore used in an attempt to prevent this perioperative fibrinolytic shutdown and so enhance graft patency. Twenty-seven patients were randomized to receive either 50 mg stanozolol or placebo intramuscularly 24 h before operation, followed by a 6 week course of either 5 mg stanozolol or placebo orally, twice daily. On the second day after operation, 10-11 MBq of autologous 111indium-labelled platelets were injected, with scanning over the graft on the 3 following days. Despite using a large depot of stanozolol, significant effects, such as raised plasminogen (P less than 0.001), reduced fibrinogen (P less than 0.001) and reduced euglobulin lysis time (P less than 0.001), were not seen until the seventh day after operation, with maximum benefit at 6 weeks. This was reflected in the 111indium-labelled platelet deposition studies. The placebo group had a progressive increase in platelet deposition on all 3 days. In contrast, those receiving stanozolol showed a lower, static picture of deposition. However, these changes did not attain statistical significance. Three patients experienced early graft thrombosis, two in the placebo group and one in the stanozolol group. Only an incomplete inhibition of the perioperative fibrinolytic shutdown was achieved. Much longer preoperative courses are thus required to allow the maximum effect to be present at the most crucial time. At present, perioperative fibrinolytic enhancement does not appear to be a practical proposition, and we must await the development of new safer and more potent agents.

Aged

Detection and characterization of arterial thromboses using a platelet-specific monoclonal antibody (P256 Fab').

Arteriography does not reliably distinguish between acute and chronic arterial occlusions. Seventeen patients with acute lower limb ischaemia were investigated by arteriography and by imaging with a platelet-specific monoclonal antibody (P256 Fab'); 20 MBq 111In-labelled P256 Fab' was administered intravenously and patients were imaged at intervals of between 20 min and 24 h. Thirteen patients were subsequently treated with intra-arterial thrombolysis. In six the images showed foci of increased uptake of 111In-labelled P256 Fab' and the corresponding arterial segment was recanalized. Patency to 30 days was maintained in four cases. Seven patients had negative scans, only four of whom achieved lysis, and two of these suffered early rethrombosis. The remaining four patients were excluded from thrombolysis by the arteriographic appearances. 111In-labelled P256 Fab' imaging can identify sites of acute arterial thrombosis and may have clinical applications in the management of peripheral vascular disease. Further studies are required to test whether the technique has a role to play in patient selection for thrombolysis.

Antibodies, Monoclonal

Anomalies in reduction-mediated technetium-99m labelling of monoclonal antibodies.

A reduction-mediated technetium-99m labelling method has been evaluated with a range of tumour-specific monoclonal antibodies. Antibodies reduced with 2-mercaptoethanol (2-ME) had free sulphydryl groups, but their number was much higher than could be accounted for by only limited intra-chain reduction of disulphide bonds. Reduced antibody could be labelled efficiently with 99mTc using an methylene diphosphonate (MDP) bone-scanning kit, although this seemed to depend on the presence of residual 2-ME in the preparations. With a carcinoembryonic antigen (CEA)-specific antibody, immunoreactivity of labelled antibody was confirmed, and after injection into nude with CEA-producing xenografts there was localisation into the tumours. Sephacryl S300 gel filtration showed the radiolabel eluting at a single discrete peak at the expected 150 kDa. However, examination of all of the labelled antibodies by polyacrylamide gel electrophoresis (PAGE) and autoradiography showed the presence of a large number of radiolabelled low molecular weight degradation products of the antibodies. These degradation products seemed to be formed in previously reduced antibodies during processing for PAGE, indicating some fragility of the reduced antibody.

Antibodies, Monoclonal

A comparison of same day and separate day injection protocols for myocardial perfusion SPECT using 99Tcm-MIBI.

Three dose administration protocols for 99Tcm-MIBI were applied to groups of 15 patients with known or suspected ischaemic heart disease. Firstly, injections were given on consecutive days, with 300 MBq at rest and 500 MBq 24 h later at exercise. Secondly, both injections on the same day with 200 MBq at rest followed 1.5 h later by 1000 MBq during exercise. Finally, both injections on the same day with 200 MBq at rest followed 1.5 h later by 600 MBq during exercise. The diagnostic accuracy was significantly better when the administrations were on separate days than when given on the same day. There was no difference in diagnostic accuracy between the two same day protocols. The same day protocols gave a significantly higher false negative reporting rate than the separate day protocol.

Adult

111In platelet deposition following peripheral arterial thrombolysis.

Streptokinase (Sk) and recombinant tissue plasminogen activator (rt-PA) have widely different effects on platelet aggregation. We have therefore undertaken a prospective evaluation of the deposition of indium-111 platelets following peripheral arterial thrombolysis. Seventeen patients were studied using autologous indium-111 labelled platelets. Patients were randomly allocated to receive 0.5 mg h-1 intra-arterial rt-PA (ten patients), or 5000 units h-1 Sk and 250 units h-1 heparin intra-arterially (seven patients). Initial uptake ratios (comparing affected limb to contra-lateral limb) at 24 h were usually low for both agents (medians: Sk 1.17; rt-PA 1.20) despite previous angioplasty or extensive thrombosis. There were minimally higher uptake ratios at 48 h and 72 h following Sk (1.64-1.45), than with intra-arterial rt-PA (0.93-1.43). Overall, two patients (one from each group) failed to achieve complete lysis or incurred early rethrombosis. Both were associated with a progressive increase in uptake ratio which was not present in those patients with successful initial lysis and continued patency at 30 days (1.18-0.94-1.19). We have been unable to demonstrate any significant difference in post-lysis platelet deposition between intra-arterial streptokinase and recombinant tissue plasminogen activator in this preliminary study. However, higher platelet deposition was associated with failure to achieve complete lysis and early rethrombosis. Concurrent therapy with antiplatelet agents may therefore be indicated in these patients.

Blood Platelets

111In-labelled leucocyte imaging in vascular graft infection.

Twelve patients with a clinical diagnosis of possible vascular graft infection have been studied over the last 3 years. All patients had their leucocytes labelled with indium-111 and gamma-camera imaging after 24 and 48 h. Subsequent management was according to established surgical techniques. Eight patients proved to have vascular graft infection and indium uptake was seen along the length of the graft in six. Two patients with open wound infections and synthetic grafts had localized uptake only on leucocyte scanning. Four patients, all of whom had negative scans were not thought to have infected grafts after further investigation using digital subtraction angiography and computed tomography scanning. These patients have been followed up for a median period of 19 months (range 5-25 months) and have remained symptom free. Initial experience with 111In-labelled leucocyte scanning has been encouraging, both in diagnosis and in planning the management of patients with graft infections.

Bacterial Infections

A comparison between visual and quantitative analysis in a prospective evaluation of labelled 111In leucocyte imaging in vascular infection.

In a continuing evaluation of 111In-oxine labelled leucocyte imaging in vascular surgery, we have studied 16 patients with a clinical diagnosis of possible vascular graft infection. We have evaluated both visual and semi-quantitative analysis of the images obtained and have interpreted these in the light of the subsequent clinical outcome. Full length or multifocal uptake was seen in six patients, all of whom eventually required graft excision with two limbs surviving, and one death. These patients had a significantly higher uptake ratio (median = 3.26) than those with either localized (median = 1.12; p = 0.0027) or negative images (median = 0.72; p = 0.0003). Of four patients showing localized uptake only, one required amputation for continuing sepsis. Six patients had negative images, and had normal DSA and CT scans. Uptake ratios could not distinguish between those with localized images and those with negative images. Computer generated vertical profiles aided separation of patients with presumed localized and negative images. Semi-quantitative analysis has proved to be a reliable method which should allow a more direct comparison of the efficacy of various investigative techniques and of the results of therapy, independent of intra-observer subjective bias.

Aged

A comparison of planar and tomographic imaging of the myocardium using 99Tcm-t-butyl isonitrile.

Oblique reconstruction tomography for stress imaging of 99Tcm-t-butyl isonitrile was performed. Oblique reconstructions, transaxial reconstructions and conventional planar images were reported by three observers. These reports were compared in 12 patients with suspected heart disease, using ECG, cardiac enzymes and coronary angiography to derive diagnostic standards. Oblique reconstruction tomography gave better agreement between the observers and more accurate diagnoses than either transaxial reconstruction or planar imaging.

Adult

The stability of 99Tcm-DTPA in an aerosol delivery system.

99Tcm-DTPA is now widely used in aerosol nebulizers for routine ventilation lung scanning. The stability of a commercially available DTPA kit has been measured when used in an aerosol delivery system and compared with the stability when stored in the parent vial according to the manufacturer's instructions. No significant breakdown was measured up to 8 h after reconstitution in the parent vial and up to 3 h when used as an aerosol. Values of the half time of clearance of DTPA aerosols in a group of 23 patients are compared with values given in the literature.

Adolescent

The biological fate of sulphur colloid.

The in-vivo behaviour of sulphur colloid has been investigated using colloids labelled with 35S as well as 99m Tc. The rates of clearance of 35S and 99m Tc from the blood, the rates of accumulation in liver and bone and the distribution of the two radioisotopes in various organs are all markedly different. The results demonstrate that although technetium is rapidly removed from the blood stream and primarily accumulated in the liver the colloid particles themselves are broken down in vivo with the release of sulphur.

Animals

The physical and chemical characteristics of sulphur colloids.

The characteristics of sulphur colloids have been investigated using colloids labelled with 35S as well as with 99mTc. The results support a model in which technetium is incorporated in the body of the particle rather than on its surface. Elemental sulphur on the surface of the particle is susceptible to attack both by sulphide ions and by protein and other materials containing --SH groups. The ready conversion of sulphur to soluble polysulphides means that sulphur colloid particles undergo conspicuous changes in diameter, both while standing in a closed vial, and on injection into body fluids. This behaviour casts doubts on the value of routine particle-size measurement as a quality control procedure.

Colloids

Mode of action of the antibacterial compound dequalinium acetate.

Dequalinium acetate is taken up rapidly by bacterial cells. Unlike the membrane-active drugs exemplified by cetrimide or chlorhexidine, its capacity for damaging the plasma membrane is low. The drug appears to penetrate quite rapidly into the cytoplasm where its effect seems to be exerted. A review of the evidence obtained in this study suggests that nucleic acid-containing components of the cell may be the prime target of this compound.

Anti-Bacterial Agents