Restoration of blood flow to an acutely ischemic lower limb may paradoxically result in systemic complications and unexpected mortality. It has been suggested that lower limb ischemia reperfusion alters gut permeability. In this study, using a rat model, we determined the effect of acute lower limb ischemia-reperfusion on mortality rate, bowel morphology, and circulating concentrations of endotoxin and the proinflammatory cytokine interleukin-6. Survival rate was compared in two groups of adult Wistar rats: (1) control group (n = 10); and (2) animals subjected to 3 hours of bilateral hind limb ischemia followed by reperfusion (n = 10). Both groups were observed under standard conditions for 4 days. In a second experiment three groups of animals were studied: (I) control (n = 12); (II) 3 hours of bilateral hind limb ischemia alone (n = 12); and (III) 3 hours of bilateral hind limb ischemia followed by 2 hours of reperfusion (n = 12). Animals subjected to bilateral hind limb ischemia followed by reperfusion had a significantly higher mortality rate (70%) than controls (0%) (p < 0.005). Morphometric assessment of the small bowel showed a significant decrease in mean mucosal thickness in the ischemia-reperfusion group compared with that in the group of controls and the ischemia-alone group (p < 0.05). Bilateral hind limb ischemia followed by reperfusion was associated with significantly increased plasma concentrations of endotoxin (p < 0. 05) and interleukin-6 (p < 0.0001) compared with that of controls and ischemia alone. These results indicate that reperfusion of the acutely ischemic lower limb is accompanied by structural changes in the gut mucosa associated with increased systemic endotoxin concentrations and cytokine activation. Mortality following reperfusion of the acutely ischemic limb may be related to a systemic inflammatory response triggered by endotoxin of gut origin.

Thirteen nuclear and cellular morphometric variables were measured in 312 cases of colorectal adenocarcinoma. All variables, except nuclear shape factors, differed significantly (P < 0.001) between normal colorectal and tumor tissue. In adenocarcinomas, epithelial nuclei in well-differentiated mucosa tended to be elliptic, while those in poorly differentiated mucosa were more spheric. Increasing values of maximum nuclear and elliptic diameter were associated with progression from none to simple tubule configuration (P < 0.001), none to easily discerned nuclear polarity (P < 0.001), and expanding growth pattern (P < 0.001). Univariate survival analysis revealed that none of the morphometric variables was significantly related to patient survival. Multivariate regression analysis showed that no morphometric variable could add significantly to a model containing the variables of patient age, Dukes stage, and tumor differentiation. Morphometry may be useful in distinguishing malignant from normal tissue and degrees of differentiation, but it is of little prognostic value in colorectal adenocarcinoma.

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Department of Electrical and Electronic EngineeringThe Queen's University of Belfast, UKAn expert system to assist in the design of different classes of linear microwave amplifiers for MIC/MMIC circuits is presented for the first time. The principal stages in the design of such a circuit are outlined and the decision to implement the expert system justified. Two important aspects of the design process are addressed ; the choice of optimum circuit topology for a given specification and the selection of a suitable FET or FETs for that topology. The overall structure of the expert system is described and its operation demonstrated using a typical amplifier design.

A framework program MADE (MMIC Automated Design Environment) (figure 1) is presented which is used in the training of undergraduate and postgraduate engineering students for the design and layout of MMIC circuits. The expert system submodules of MADE; ADAM, GALEDA and GALA are' described. Starting from a performance specification, the user is advised' on microwave circuit topology selection, design of custom and standard cells including foundry -specific parasitics and optimum layout to minimise real estate usage and avoid Intercomponent coupling. CIRCUIT DESiQNUndergraduate and postgraduate students at Queens University are familiar with microwave design concepts. They do not, however, appreciate the advantage offered by modern microwave CAD tools in design. A student will usually be presented with a circuit specification such as a broad band amplifier for example. lnstead of producing a