CLINICAL PROGRESS Fever Pathogenesis and Circulatory Changes

F EVER has been recognized as a common and reliable sign of disease for many centuries, and many of the associated cir-culatory chancges have loneg been known; the cold pale skin, the subsequent warmth and flushing, and the rapid pulse were well-defined clinical signls loneg before the intro-duction of the thermometer. The first experimental approach to the nature of the stimulus responsible for fever was made at the middle of the last century, when several German workers produced fever in experimental animals by the injec-tion of pus aiid blood from other infected animals. As they were unaware of the nature and danguers of bacterial contamination, it is difficult to imiterpret their results. One cannot but be inipressed by the fact that the same general methods of study are still employed at the present time; some of this early work is described in a recent review.1 In 1875, Von Ljieberiueister2 concluded that in fever the body temperature was regulated at an abnormally high level, but that the tempera-ture-regulatingr mechanism remained intact and efficient. This hypothesis has been sub-stalitiated by numerous experiments, and though it is (learly invalid ini the case of the pyrexia associated with brain damage, it represents the view generally held at present. Despite some evidence to the con-trary,:3 the comnmonly held comncept of fever as a chang*ye in the settimg of a central thermo