The local effects of intracutaneous injections into humans of 1-3 nmol of five products of arachidonic acid metabolism, leukotrienes (LT) C4, D4, E4, and B4 from the 5-lipoxygenase pathways and prostaglandin (PG) D2 from the cyclooxygenase pathway, were assessed clinically and histologically. In equimolar concentrations, LTC4, LTD4, and LTE4, elicited erythema and wheal formation, in which a wheal with central pallor was present up to 2 hr, and the erythema persisted as long as 6 hr. PGD2 elicited a wheal that lasted up to 1 hr and erythema that lasted up to 2 hr. The dermal vascular sites affected by LTD4 and PGD2 included capillaries, superficial and deep venules, and arterioles. LTB4 elicited a transient wheal and flare, followed in 3-4 hr by induration that was characterized by a dermal infiltrate comprised predominantly of neutrophils. The combination of LTB4 and PGD2 elicited tenderness and increased induration associated with a more intense neutrophil infiltration. Thus, the products of the 5-lipoxygenase pathway of arachidonic acid metabolism in nanomole amounts can induce cutaneous vasodilation with edema formation and a neutrophil infiltrate, and these responses are enhanced by a cyclooxygenase pathway product, PGD2.
The exploitation of phase contrast appears to offer the tantalising possibility of creating the biggest change in medical x-ray imaging since the invention of computed tomography. A considerable number of experiments performed by researchers across four continents have produced some extraordinary images. These images have demonstrated greatly enhanced contrast over conventional methods revealing soft tissue discrimination at micron scale resolutions. Contrast improvements can be achieved at doses rather less than those required by conventional x-ray imaging. The use of synchrotrons has revealed the possibilities offered by these techniques but unfortunately the application of these ideas in a clinical context requires that technology be pushed to its limits in a number of areas including x-ray sources, optics and detectors. The current state of the art is reviewed.
Aeration of the lung and the transition to air-breathing at birth is fundamental to mammalian life and initiates major changes in cardiopulmonary physiology. However, the dynamics of this process and the factors involved are largely unknown, because it has not been possible to observe or measure lung aeration on a breath-by-breath basis. We have used the high contrast and spatial resolution of phase contrast X-ray imaging to study lung aeration at birth in spontaneously breathing neonatal rabbits. As the liquid-filled fetal lungs provide little absorption or phase contrast, they are not visible and only become visible as they aerate, allowing a detailed examination of this process. Pups were imaged live from birth to determine the timing and spatial pattern of lung aeration, and relative levels of lung aeration were measured from the images using a power spectral analysis. We report the first detailed observations and measurements of lung aeration, demonstrating its dependence on inspiratory activity and body position; dependent regions aerated at much slower rates. The air/liquid interface moved toward the distal airways only during inspiration, with little proximal movement during expiration, indicating that trans-pulmonary pressures play an important role in airway liquid clearance at birth. Using these imaging techniques, the dynamics of lung aeration and the critical role it plays in regulating the physiological changes at birth can be fully explored.
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