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Biomedical subjects

R F Wood

Publications and source records attributed to R F Wood.

At least 19 recordsLinked to original sources

Introduction of a partial shift system for house officers in a teaching hospital.

OBJECTIVES: (1) To introduce a partial shift system to reduce the hours of work of preregistration house surgeons to an average of 64 a week to comply with the New Deal for junior doctors; (2) to test linking the partial shift concept to an existing structure of "on call" firms. DESIGN: Formal assessment after three months of a pilot partial shift system for eight house surgeons on three firms instituted on 1 November 1991, followed by questionnaire and interview evaluation at three and six months of a revised system implemented on 1 February 1992. SETTING: Department of general surgery at St Bartholomew's Hospital, London. SUBJECTS: 24 house surgeons attached to three surgical firms. RESULTS: In eight weeks each house surgeon worked one week (five shifts) of night duty, one week of "cover" (afternoon and evening) duty, and six weeks of normal daytime hours. Each weekday a house surgeon from the firm on call worked an extended daytime on call shift until 10 pm. Weekend duties were split between two house surgeons from the firm on call. A computer generated graphical display of the rota was used to facilitate leave planning. Average working hours were reduced to below 64 per week, including prospective cover, without detriment to patient care and educational standards. Within the shift system individual house surgeons could be on call with their own firm by day and at weekends. Opinions were equally divided among junior staff as to their preference for either on call or partial shift systems. CONCLUSIONS: The principles of this partial shift system are generally applicable and the model can readily be adopted by district general hospitals.

Attitude of Health Personnel

Lasers in surgery.

In January 1991 the winter meeting of the Surgical Research Society was held at St. Bartholomew's Hospital and the Institute of Education, London. During the meeting a symposium was held entitled 'Shedding light on lasers'. Speakers addressed the general principles of lasers, laser-tissue interactions and the applications of lasers in gastro-enterology and in vascular disease. This was followed by an open discussion of the current indications, complications and outcome, together with future possible applications for lasers in medicine.

Arterial Occlusive Diseases

Laser-assisted angioplasty for arterial occlusion of the lower limb: initial results and follow-up.

A flashlamp-pumped pulsed dye laser operating at either 480 or 504 nm, coupled to an integral ball-tipped optical fibre, was used to recanalize occluded lower limb arteries. All channels created by the laser were augmented with balloon dilatation. We have treated 78 limbs in 71 patients; 46 limbs (59 per cent) had rest pain and 22 (48 per cent) of these had tissue loss. The median occlusion length was 18 (range 0.5-58) cm. Technical success was achieved in 58 limbs (74 per cent) with clinical success in 46 (59 per cent). Success rates fell with increasing length of occlusion. Two patients died in the perioperative period. A subgroup of 22 patients with marked discrete arterial calcification had a lower technical success rate than the subgroup without calcification (50 per cent versus 84 per cent, P less than 0.01). Both subgroups displayed a similar pattern of reclosure during follow-up. The cumulative patency rate after technical success was 67 per cent at 6 months and 45 per cent at 12 months. Forty-six (59 per cent) limbs avoided bypass surgery or amputation. Laser-assisted angioplasty may offer an alternative to femoropopliteal bypass, although the former procedure is not as durable.

Adult

Persistence of allogeneic cells in graft and host tissues after small bowel transplantation.

Small bowel transplantation is associated with a significant risk of graft versus host disease owing to the large amount of organized lymphoid tissue within the graft. This study assessed whether graft lymphoid cells could persist in the long term following fully allogeneic small bowel transplantation when graft rejection was prevented by cyclosporin immunosuppression. Transplantation was carried out between PVG and DA strains of rat. Cyclosporin (15 mg/kg) was given daily from transplantation, and groups of animals were studied at 28 and 56 days after grafting. The proportions of donor- and recipient-derived cells in the graft and in the host gut and lymphoid tissues were assessed using immunohistochemical tissue staining and monoclonal antibodies specific for cells expressing class I antigens from the two strains of rat. Results demonstrated a persisting population of graft-derived T cells which were capable of migration to the host. Therefore, there may be a long-term risk of graft versus host disease after small bowel transplantation under cyclosporin immunosuppression.

Animals

Potential candidates for small bowel transplantation.

The number of potential candidates for small bowel transplantation in the UK is unknown. Potential recipients are those with irreversible small intestinal failure, including those treated with permanent parenteral nutrition. This study of one of the largest groups of patients receiving such nutrition identified ten of 25 adult patients as possible recipients. The remaining 15 were considered unsuitable, mainly because of multiple previous abdominal operations or abscesses. Extrapolation of these data to national figures on the incidence of irreversible small intestinal failure suggests that each year up to 20 new adult patients in the UK might benefit from small bowel transplantation.

Adolescent

Ex vivo perfusion of intestinal allografts with anti-T cell monoclonal antibody/ricin A chain conjugates for the suppression of graft-versus-host disease.

The removal of T lymphocytes from intestinal allografts prior to transplantation would prevent graft-versus-host disease and might also weaken the unusually severe rejection response mounted by graft recipients. Ex vivo perfusion by monoclonal antibody-toxin conjugates represents a potentially ideal approach to achieve this goal. Monoclonal antibody-toxin conjugates were prepared by coupling the mouse anti rat CD5 antibody MRC OX19 to the A chain of ricin. The resultant conjugate contained 1 or 2 ricin A chain molecules per molecule of immunoglobulin and had high selective toxicity for rat T lymphocytes. Following ex vivo perfusion of the small intestine, the mesenteric lymph nodes and Peyer's patches were removed and the level of penetration of the MRC OX19 antibody was assayed by immunohistological techniques. In lymph nodes, there was ready access of the antibody to the medulla, and to a lesser extent to the B cell areas of the cortex. However, only the T cells in the peripheral regions of the paracortex were stained, suggesting that the paracortex was resistant to penetration by blood-borne antibody, and was being stained only by diffusion from the lymph node medulla. Some penetration of the antibody also occurred in the immediate vicinity of the postcapillary venules. In the Peyer's patches, staining was seen in the germinal centers, but not at all in the T cell areas. The addition of agents such as histamine to the perfusate to increase vascular permeability did not alter this picture. These studies suggest the presence of a potentially interesting resistance to penetration of the paracortex of the lymph node by blood-borne substances. Nevertheless, sufficient penetration occurred to influence favorably the course of GVD disease following ex vivo perfusion prior to transplantation of the donor intestine with the MRC OX19-ricin A chain conjugate.

Animals

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