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Biomedical subjects

R F Wood

Publications and source records attributed to R F Wood.

At least 55 records · Page 3Linked to original sources

Method for diagnosing rejection in small bowel transplantation.

Diagnosis of rejection in small bowel transplantation by the identification of a host-cell infiltrate is hampered by the physiological trafficking of host lymphocytes to the 'gut-associated lymphoid tissue' of the graft. This study compared physiological host-cell infiltration of small bowel grafts with that occurring in rejection and stable immunosuppression. Physiological host-cell infiltration, where the graft does not present an immune stimulus to the host, was assessed by transplanting bowel from DA to (DA x PVG) F1 hybrid rats. The extent of host-cell infiltration was determined by immunohistochemical analysis. In the lamina propria, considerable infiltration by host cells was seen, although it was significantly less than that in rejection or stable immunosuppression. By contrast, host cells were seen in the intraepithelial compartment only in rejection. Host-cell infiltration in the absence of an allogeneic stimulus suggests that histological identification of host cells in the lamina propria is not necessarily indicative of rejection. However, the presence of host cells in the intraepithelial compartment is specific for rejection in small bowel transplantation.

Animals↗

Low-dose aspirin fails to inhibit increased platelet reactivity in patients with peripheral vascular disease.

A study was performed to evaluate the effect of low-dose aspirin (75 mg/day) on platelet reactivity in patients with peripheral vascular disease. Platelet function was measured in 31 patients with advanced peripheral vascular disease requiring surgery. Shear-induced haemostasis and collagen-induced thrombus formation were used as indicators of platelet reactivity. They were measured in non-anticoagulated fresh whole blood samples ex vivo using a haemostatometer. Results were compared with those from 30 age- and sex-matched controls. Shear-induced haemostasis and collagen-induced thrombus formation were also measured in 18 of the 31 patients before the start of aspirin administration (before operation) and 1 week after surgery. Patients with advanced peripheral vascular disease were found to have increased platelet reactivity with a mean(s.e.m.) shear-induced haemostasis index of 1977(180) mmHg s compared with a control value of 3161(234) mmHg s (P < 0.001) and a mean(s.e.m.) collagen-induced thrombus formation index of 3980(460) mmHg s compared with a control value of 5350(420) mmHg s (P = 0.02). Perioperative low-dose aspirin failed to inhibit platelet function in patients with peripheral vascular disease.

Aged↗

Beta carotene uptake into atherosclerotic plaque: enhanced staining and preferential ablation with the pulsed dye laser.

The yellow color of atherosclerotic plaque is due to the presence of carotenoids, which absorb light between 430-530 nm and account for the preferential ablation of plaque by the pulsed dye laser operating at 480 nm. This study was designed to examine tissue uptake of beta-carotene and the effect of uptake on arterial plaque ablation. Forty-two atherosclerotic NZW rabbits were given intravenous beta-carotene at a dose of 40 mg/kg, twice weekly and killed between 1 hour and 28 days after the initial injection. beta-carotene was not detected in control specimens but was significantly greater in plaque than in normal wall at all time points following beta-carotene injection (P < 0.04 Mann Whitney U test). The ablation threshold was significantly lower in beta-carotene treated plaque than in untreated plaque or normal arterial wall (P < 0.01, Fisher's exact test). In this model beta-carotene is preferentially taken up into arterial plaque, resulting in increased absorption of laser radiation at 480 nm and enhanced tissue ablation.

Adipose Tissue↗

The effect of rejection and graft-versus-host disease on small intestinal microflora and bacterial translocation after rat small bowel transplantation.

Bacterial translocation and the development of sepsis after small bowel transplantation may be promoted by immunological damage to the intestinal mucosa or by quantitative and qualitative changes in intestinal microflora. This study assessed the effects of rejection, graft-versus-host disease (GVHD) and immunosuppression on intestinal microflora and bacterial translocation after heterotopic rat small bowel transplantation. Isografts, allografts with and without CsA immunosuppression, and the semi-allogeneic parent to the F1 hybrid GVHD model were studied. Intestinal microflora in graft and host loops and bacterial translocation to host organs and the graft mesenteric lymph node were determined. Bacterial colonies were counted and individual colonies identified using API 20E nutrient and fermentation indicator techniques. Colony counts in isografts and allografts were significantly higher than in the native intestine, whereas there was a massive overgrowth in the native intestine in the GVHD group. The species profile for the host and graft loops was similar in animals that had received isografts, allografted animals receiving CsA, and animals undergoing GVHD. However, there was a large increase in Staphylococcus epidermidis in animals with rejection. Bacterial translocation was not detected in isografted animals, but was observed in all other animal groups, with S. epidermidis being the most prevalent organism. These findings demonstrate that rejection and GVHD are associated with shifts in intestinal microflora toward potentially pathogenic organisms and that bacterial translocation into recipient tissues poses a major threat for the development of sepsis.

Animals↗

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↗