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Biomedical subjects

R F Wood

Publications and source records attributed to R F Wood.

At least 37 records · Page 2Linked to original sources

Blood flow in the lower limb after balloon angioplasty of the superficial femoral artery.

Using duplex ultrasonography lower-limb blood flow measurements were obtained in 20 patients with intermittent claudication. Assessments of flow were made in the common femoral artery, profunda femoris artery (PFA) and superficial femoral artery (SFA) before and after angioplasty for stenoses of short segments of the SFA. Blood flow was measured at rest and after exercise on a cycle ergometer. Collateral flow was calculated using an established mathematical model. Results were compared with the ankle:brachial systolic pressure index (ABPI) after exercise. Although there was no overall increase in resting limb blood flow, an increase in mean(s.d.) SFA flow from 148(79) to 312(94) ml min-1, with a concomitant decrease in PFA flow from 224(84) to 98(43) ml min-1 was noted 1 week after angioplasty (P < 0.05). At rest there was an increase in mean(s.d.) ABPI from 0.62(0.12) to 0.89(0.23) (P < 0.05). Collateral flow was estimated to have decreased from 186(34) to 18(8) ml min-1; the pattern of change in flow was similar after exercise. Angioplasty of the SFA remains controversial because of the risk of restenosis. The above methodology allows assessment of whether patients can re-establish collateral flow or whether limb blood flow will be significantly compromised if restenosis occurs.

Aged↗

Observer variability in volumetric blood flow measurements in leg arteries using duplex ultrasound.

Duplex ultrasound volumetric flow measurements have not found a major clinical use because of variability caused by errors in estimating cross-sectional area (CSA) and in measuring time averaged mean velocity (TAMeV). We determined inter- and intraobserver variation in volumetric blood flow measured at rest in the common femoral artery (CFA) and its main branches, the superficial femoral (SFA) and profunda femoris (PFA) arteries, in 20 normal subjects. The product of TAMeV and CSA was taken as volumetric flow. The coefficient of variation of TAMeV was consistently greater than that of CSA. Interobserver variation for blood flow (16.2%, 20.2% and 40.3% for CFA, SFA and PFA, respectively) was larger than intraobserver variation (13.0%, 15.1%, 21.2%). In conclusion, these data define the minimum changes in VQ that can be realistically detected and indicate that, with modern duplex Doppler equipment, volumetric flow can be used as a reliable haemodynamic measure for monitoring patients before and after surgical or radiological intervention.

Adult↗

Haemodynamic and metabolic responses of the lower limb after high intensity exercise in humans.

This study assessed blood flow in the common femoral, superficial femoral and profunda femoris arteries, the effects of vasodilator metabolites and changes in blood pressure and pulse during recovery after high intensity exercise (Wingate test). Mean common femoral artery flow increased sevenfold in response to the exercise. The subsequent decline in mean common femoral artery flow was mono-exponential with a mean time constant of 19 min. The post-exercise increase in profunda femoris artery flow (ninefold) was significantly greater than the superficial femoral artery flow (fourfold, P < 0.05). Systolic blood pressure and heart rate decreased monotonically throughout recovery. In contrast, diastolic blood pressure showed a significant fall below baseline at 3 min (P < 0.05) with a return to baseline at 60 min. The greatest drop below baseline (approximately 20 mmHg) occurred around 7 min. Lactate reached a maximum of 13.6 +/- 2.3 mmol -1 at 8 min (P < 0.05) and was still significantly above baseline at 60 min. pH remained below 7.2 until 20 min of recovery. The results demonstrate that following high intensity exercise, blood flow to the limbs appears to be controlled by complex interactions of various vaso-active metabolites, each contributing proportionally more at different times during recovery.

Adult↗

CD44 expression in rejecting rat small bowel allografts.

CD44 is a widely expressed cell surface protein that recognizes multiple ligands and is involved in extra- and intercellular adhesion. The precise role of CD44 in immune interactions is currently unknown, but it is believed to be a homing receptor involved in lymphocyte trafficking and inflammatory responses. This study investigated CD44 expression in intestinal tissue after heterotopic rat small bowel transplantation and assessed the effect of transplantation on intestinal epithelial cell proliferation using an antibody to the nuclear activation Ag Ki67. Lamina propria and intestinal epithelial cell expression of CD44 was graded blindly by five observers, and villus epithelial cells were noted as being positive or negative for Ki67 staining. CD44 expression was high in the lamina propria of both allografted and isografted animals; however, there was no significant difference between the two groups. In contrast, the expression of CD44 on the villus epithelium was greater in allografted animals and progressed toward the villus tips as rejection developed, declining thereafter because of loss of villus integrity. Ki67 positivity was also greater in allografted animals but did not progress toward the villus tip. This is the first reported observation of CD44 expression on intestinal epithelium that is not restricted to the crypts. The findings indicate the involvement of CD44 in the rejection process and demonstrate changes in the proliferative profile of rejecting small intestinal epithelium. Further studies into adhesion molecules, such as CD44, may help to improve understanding of graft failure and promote the development of new therapeutic approaches for controlling and preventing graft rejection.

Animals↗

Differential expression of adhesion molecules during rat small bowel allograft rejection.

The adhesion molecules intercellular adhesion molecule 1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1) (alpha and beta chains), and very late activation antigen-4 (VLA-4) have an essential role in cell-cell interactions and the initiation of immune responses. This study used an indirect immunoperoxidase technique to investigate the expression of these molecules in the lamina propria of allografts and isografts after heterotopic rat small bowel transplantation. Normal untransplanted small bowel served as additional controls. Overall, ICAM-1 and LFA-1 alpha expression was significantly higher in allografts, although there was variable expression of these molecules in isografted animals. There were temporal differences in the expression of ICAM-1 and LFA-1 alpha in that increased ICAM-1 expression was more pronounced in the the early posttransplant period, whereas there was a progressive increase in LFA-1 alpha as rejection developed. In contrast, there was no difference between allograft and isograft expression of LFA-1 beta and VLA-4. This study has demonstrated a preferential increase in adhesion molecule expression with developing rat small bowel allograft rejection and suggests that adhesion molecules are involved in the development and progression of allograft rejection. Although the observed differences in antigen expression are not as marked as those previously reported in other organ transplants, appropriate adhesion molecules may present suitable targets for immunotherapeutic protocols after small bowel transplantation.

Animals↗

Flow cytometric analysis of peripheral blood lymphocyte subset light scatter characteristics as a means of monitoring the development of rat small bowel allograft rejection.

This investigation used flow cytometry to monitor peripheral blood lymphocyte morphology after rat small bowel transplantation. Preliminary studies demonstrated that in vitro activated peripheral blood lymphocytes exhibited increased cell size and granularity as measured by flow cytometric analysis of forward (FSc) and side (SSc) light scatter characteristics. The formation of distinct 'activated' light scatter regions by such lymphoblastoid transformation occurred concomitantly with up-regulated p55IL-2R expression. Heterotopic small bowel transplantation was performed between PVG donor and DA recipient rats without immunosuppression. Animals receiving isografts served as controls. Peripheral blood lymphocyte subsets were identified using appropriate MoAbs, and the light scatter characteristics of each cell subset were determined by backgating strategies. Increased proportions of activated alpha/beta T cell receptor (TCR)-positive cells could be detected in allografted animals as early as day 2 post-transplantation. B cells showed peak activation by day 4, at which time the proportion of activated cells was over two-fold greater than that seen in untransplanted animals--few activated B cells were detected in isografted animals. Resting natural killer (NK) cell light scatter regions only partially overlap with those of resting T and B lymphocytes, but in allografted animals almost the entire NK population fell outside the resting lymphocyte gate by day 2 post-transplantation, an activation state which was maintained until day 4. These findings associate peripheral blood cell subset lymphoblastoid transformation with developing small bowel allograft rejection. Importantly, changes were detected early and prior to the onset of overt rejection. These data suggest that analysis of peripheral blood lymphocyte light scatter properties may provide an insight into in vivo immune status after small bowel transplantation.

Animals↗

Activation antigen expression on peripheral blood neutrophils following rat small bowel transplantation. NKR-P1 is a novel antigen preferentially expressed during allograft rejection.

This study used flow cytometric analyses to monitor activation antigen expression (MHC class II; interleukin-2 receptor, p55IL-2R and 3.2.3/NKR-P1 antigen) on peripheral blood neutrophils following rat small bowel transplantation. The rat 3.2.3 antigen is a member of the NKR-P1 family of natural killer (NK) cell-associated molecules, which are expressed at high levels on NK cells and lymphokine-activated killer cells, and low levels on at least one T cell subset. Peripheral blood neutrophils in normal animals express very low or undetectable levels of NKR-P1. Detectable levels of NKR-P1 were induced as early as day 1 following small bowel transplantation in all allografted animals, whereas expression was only rarely detected in isografted animals. In addition, NKR-P1 density was significantly higher in allografted animals and was maintained as rejection developed. MHC class II and p55IL-2R expression was also induced following transplantation. The mechanisms of induction and functional relevance of NKR-P1 expression on neutrophils remain to be defined. However, the concomitant increased expression of MHC class II and p55IL-2R suggest NKR-P1 to be a neutrophil activation marker and implicate a potential role for NKR-P1+ neutrophils in small bowel allograft rejection. This hypothesis is further supported by the loss of detectable peripheral blood neutrophils only with developing rejection. Flow cytometric analysis of neutrophil activation antigen expression may be useful for monitoring human small bowel transplant recipients.

Animals↗

Effect of small bowel transplantation, denervation and ischaemia on rat intestinal microflora.

The effects of denervation and warm ischaemia on quantitative and qualitative changes in small intestinal microflora following rat heterotopic small-bowel isotransplantation were assessed. Animals with Thiry-Vella fistula, but without transplants, acted as controls. Thirty and 40-fold increases in bacterial colony counts were seen in the isografts compared to controls at 2 and 7 days, respectively (P < 0.05). Aerobic faecal organisms predominated at 2 and 7 days, but an overgrowth of Flavobacterium meningosepticum occurred at 28 days in the transplanted and host bowels. The effect of warm ischaemia on intestinal microflora was assessed by the application of a microvascular clamp to the superior mesenteric artery for 90 min. The effect of denervation was assessed following microsurgical division of all nervous tissue around the superior mesenteric artery. After 7 days, lengths of jejunum and ileum were removed and intraluminal microflora assessed. The number of bacterial colonies isolated from the ileum in the warm ischaemia group was six times greater than the number in the control group, whereas no significant changes were seen in the upper bowel. In contrast, denervation led to a slight, but consistent, decrease in colony counts. These findings suggest that the increase in bacterial numbers in an isografted small bowel primarily results from warm ischaemia rather than from mesenteric denervation, and that physical aspects of the procedure may affect the development of sepsis following small-bowel transplantation.

Animals↗