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Biomedical subjects

R F Wood

Publications and source records attributed to R F Wood.

At least 73 records · Page 4Linked to original sources

Reduction of graft-versus-host reactivity after small bowel transplantation: ex vivo treatment of intestinal allografts with an anti-T cell immunotoxin.

A specific T lymphocyte immunotoxin was used to pre-treat small bowel grafts in an attempt to prevent graft-versus-host (GVH) reactivity and GVH disease in a rat transplant model. The immunotoxin used was a conjugate of the anti-CD5 MoAb MRC OX-19 with ricin A chain. The grafts were perfused ex vivo with a standard solution of immunotoxin followed by incubation at 4 degrees C for 1 h before transplantation. In a semi-allogeneic strain combination (parent to F1 hybrid offspring) graft treatment with immunotoxin led to a prolongation of recipient survival compared with groups receiving similar transplants without immunotoxin treatment. An additive effect on survival was observed when the host was treated with cyclosporin. The effect of immunotoxin was greater than that of mesenteric lymphadenectomy in increasing host survival. The effect of graft treatment with the immunotoxin on cellular migration from graft to host lymphoid tissues was assessed in fully allogeneic transplantation (PVG to DA). Host lymphoid tissues were subjected to immunohistochemical analysis using a MoAb specific for donor class I MHC antigens. Graft treatment with the immunotoxin led to a significant decrease in the number of graft cells found in host lymphoid tissues 7 days after transplantation. However, this effect was less marked than that achieved by graft mesenteric lymphadenectomy. With our current protocol graft treatment with a specific T cell immunotoxin can significantly reduce but not abolish GVH reactivity in rat small bowel transplantation.

Animals↗

Comparison of duplex ultrasonography and venography in the diagnosis of deep venous thrombosis.

Sixty-five patients with suspected deep venous thrombosis (DVT) in 68 limbs were entered consecutively into a study to compare venography with duplex ultrasonography scanning. Both tests were performed on 64 limbs, venography being contraindicated in four. Overall, duplex scanning correctly identified 86 per cent of DVTs diagnosed on venography and correctly excluded 80 per cent with negative venograms. Nearly all errors arose in the diagnosis of calf DVT. In the femoral vein duplex scanning had a specificity of 100 per cent and a sensitivity of 95 per cent. In addition, duplex scanning provided data on the limb not undergoing venography. Of 55 limbs that underwent bilateral duplex scanning, five had thrombus in the femoropopliteal segment and a negative contralateral venogram. In addition, three Baker's cysts were diagnosed. Duplex scanning can be used in patients in whom venography is contraindicated and may also provide information about the contralateral limb. We regard femoropopliteal duplex scanning as sufficiently accurate that treatment can be initiated on the basis of the scan. Duplex scanning should replace venography as the standard method of diagnosing femoropopliteal DVT; radiographic studies should now be required only when the scan result is in doubt.

Evaluation Studies as Topic↗

Graft versus host disease in small bowel transplantation.

Quantities of organized lymphoid tissue in small bowel allografts may cause graft versus host disease (GVHD) following transplantation. This study examines the effect of graft mesenteric lymphadenectomy on development of GVHD following small bowel transplantation in rats. GVH reactivity was assessed by measuring the degree of graft cell emigration to the host. In the PVG to DA strain combination, graft mesenteric lymphadenectomy led to a significant reduction in graft cell colonization of host lymphoid tissues from 40-50 per cent to 25-35 per cent. Transplantation from PVG to (PVG x DA)F1 hybrids caused fatal GVHD within 21 days whereas when DA donors were used survival was over 30 days. When mesenteric lymphadenectomy was performed on PVG donors, host survival increased by only 3-4 days. Mesenteric lymphadenectomy in DA donors led to long-term recipient survival with no GVHD. Intensity of GVHD following rat small bowel transplantation is a strain-dependent phenomenon and graft mesenteric lymphadenectomy does not always prevent GVHD. The mucosa may have an important immunological role.

Animals↗

Small bowel transplantation: future prospects.

The mesenteric lymph nodes and Peyer's patches of the small bowel present a significant target for immune attack in rejection. In addition they have the potential to proliferate and cause graft-versus-host disease (GVHD). Immune-mediated impairment of mucosal barrier function will allow translocation of bacteria from the gut lumen into the blood stream. This factor, with the development of septicaemia, was probably responsible for the majority of deaths in early clinical cases treated with azathioprine and prednisolone. In the experimental situation GVHD and rejection can be studied as separate entities in transplants between parental strain rats and F1 hybrids. The use of immunohistochemical staining with strain specific monoclonal antibodies has enabled the migration pattern of lymphocytes to be studied. Within 24 h of transplantation donor lymphocytes can be detected in the spleen and mesenteric lymph nodes of the recipient. This cell transfer is clearly effected through the blood stream as the severed lymphatics of the grafted bowel take at least 7-10 days to regenerate and from connections with the recipient lymph system. At a practical level impairment of normal lymphatic drainage may cause problems with the absorption of fats and fat-soluble molecules such as cyclosporin. Denervation of the bowel also presents a problem in the initial phase after transplantation, with hypersecretion from the crypts causing diarrhoea. Since the introduction of cyclosporin a small number of successful human transplants have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of renal ischemia on cyclosporine clearance in rabbits.

The renal handling of cyclosporine was studied in ischemically damaged kidneys in New Zealand White rabbits and nonischemic control animals. CsA, 25 mg/kg/day, was administered intravenously for 10 days starting with the day of operation. Blood CsA (B CsA) was higher in the ischemic group compared with the controls (median: 285 micrograms/L, range 95-785 micrograms/L vs. 170 micrograms/L, range 110-185 micrograms/L, P = 0.05) on day 1 after operation. B CsA dropped rapidly to a level equivalent to the controls by day 4 (median: 105 micrograms/L, range 60-280 micrograms/L vs. 195 micrograms/L, range 70-215 micrograms/L, P = NS). Median CsA clearance (C CsA) as a percentage of creatinine clearance (C Cr) was some ten-fold greater in the ischemic animals (6.32%, range 2.93-18.41% vs. 0.55%, range 0.13-0.78%, P less than 0.001) on day 1. The ratio gradually declined, approaching the value in controls by day 10 (0.86%, range 0.24-7.21% vs. 0.23%, range 0.16-0.73%, P = 0.05). The data suggest that renal impairment has an important effect on CsA blood levels. In the clinical situation this may be of particular importance during both oliguria and the recovery from acute tubular necrosis.

Animals↗