Theodore E. Woodward

Preliminary Report on the Beneficial Effect of Chloromycetin in the Treatment of Typhoid Fever.

Excerpt A new antibiotic Chloromycetin has been clinically tested in the treatment of typhoid fever and has been found to exhibit significant chemotherapeutic effects. A description of the results ...

Concepts of Fever: Recent Advances and Lingering Dogma

Fever has been a preoccupation of clinicians since medicines beginning. One might therefore expect that basic concepts relating to this physiological response would be well delineated and that such concepts would be widely known. In fact, only in the past several decades has the febrile response been subjected to scientific scrutiny. As a result of recent scientific investigation, modern concepts have evolved from a perception of fever as nothing more than a rise in core temperature to one in which fever is recognized as a complex physiological response characterized by a cytokine-mediated rise in temperature, as well as by generation of acute-phase reactants and activation of a panoply of physiological, endocrinologic, and immunologic systems. The average clinician appears to have little more than a regrettably rudimentary knowledge of these modern concepts of fever. This symposium summary considers many such concepts that have immediate relevance to the practice of medicine.

The history of epidemic typhus

Few infectious diseases have influenced human civilization to the same degree as louse-transmitted typhus. Rickettsia prowazekii continues to strikes tens to hundreds of thousands of persons who live with war, famine, crowding, and in squalid conditions associated with social unrest, with mortality rates in excess of 10% to 15%. Historical documents confirm that such devastation has been a continuous feature of human existence to the extent that typhus has been a major determinant in the outcome of many wars, altering human history in its wake-despite incomplete knowledge of its precise origin. In the twenty-first century, circumstances are still conductive for outbreak; the emerging threat of bioterrorism raises justifiable concerns that typhus could affect civilization just as greatly in the future as it has in the past.

The role of endotoxin during typhoid fever and tularemia in man: IV. The integrity of the endotoxin tolerance mechanisms during infection

Volunteers infected with Salmonella typhosa develop a remarkable hyperreactivity to the pyrogenic and subjective toxic activities of homologous (S. typhos) and heterologous (Pseudomonas) endotoxins. The present studies quantitate this augmented reactivity and demonstrate by three differing approaches that significant tolerance to these endotoxins can be readily induced within the framework of the hyperreactive state. Thus, (a) tolerance induced before illness by repeated daily intravenous injections of the endotoxins remained demonstrable during overt illness, (b) daily intravenous injections of the endotoxins begun during overt illness evoked progressively increasing tolerance, and (c) continuous intravenous infusions of S. typhosa endotoxin during illness rapidly induced a pyrogenic refractory state. Despite unequivocal activation of the endotoxin tolerance mechanisms by any of the above methods, the febrile and toxic course of typhoid fever proceeded unabated. Similarly, in other volunteers with Pasteurella tularensis infection, continuous intravenous infusions of S. typhosa endotoxin evoked initial hyperreactive febrile and subjective toxic responses followed by rapid appearance of a pyrogenic refractory state without modification of the underlying clinical illness. These observations suggest that circulating endotoxin plays no major role in pathogenesis of the sustained fever and toxemia during typhoid fever and tularemia in man. The mechanisms responsible for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia were further investigated. Low grade endotoxemia, nonspecific effects of tissue injury, impaired ability of the reticuloendothelial system to clear circulating endotoxin, and production of cytophilic antibodies capable of sensitizing leukocytes to endotoxin did not appear responsible. Inflammatory reactions to intradermal S. typhosa endotoxin increased significantly during typhoid fever. However, since no such dermal hyperreactivity developed to Pseudomonas endotoxin during typhoid fever nor to S. typhosa endotoxin during tularemia, the systemic hyperreactivity to bacterial endotoxins during typhoid fever and tularemia could not presently be ascribed to enhanced levels of acquired hypersensitivity.

Q Fever Hepatitis

Abstract Hepatic involvement was appraised in three individuals with Q fever. One patient presented with moderately severe hepatitis without pulmonary involvement, whereas the other two were volunt...

VIRAL AND RICKETTSIAL CAUSES OF CARDIAC DISEASE, INCLUDING THE COXSACKIE VIRUS ETIOLOGY OF PERICARDITIS AND MYOCARDITIS

Excerpt INTRODUCTION Pyogenic pericarditis is well known and, in contrast to the benign, nonspecific types, is frequently fatal. Rheumatic carditis is common and readily recognized, as a rule. Myoc...

Management of Typhoid Fever and Its Complications

Excerpt Fifteen years have elapsed since chloramphenicol was first employed for the treatment of typhoid fever. During this period, it has become the accepted drug for the control of the acute typh...

Chloromycetin and aureomycin; therapeutic results.

Excerpt During the last 18 months two new antibiotics appeared which have greatly extended specific therapy in the group of infectious diseases. It is of interest that our earliest specific remedie...

THE TREATMENT OF ROCKY MOUNTAIN SPOTTED FEVER WITH CHLOROMYCETIN

Excerpt The demonstrated efficacy of Chloromycetin in the treatment of human cases of scrub typhus1encouraged belief that this new antibiotic might likewise prove effective in the therapy of Rocky ...

COMPARATIVE EFFICACY OF CHLORAMPHENICOL, AMPICILLIN, AND CO-TRIMOXAZOLE IN THE TREATMENT OF

Two clinical trials were conducted to compare the efficacy of 3 antimicrobial agents often recommended for the treatment of typhoid fever. Chloramphenicol was more effective than parenteral ampicillin or oral co-trimoxazole (trimethaprim/sulphamethoxazole) in reducing the duration of fever. Oral chloramphenicol was more effective than parenteral chloramphenicol probably because oral doses resulted in higher blood concentrations of the drug. However, parenteral chloramphenicol was given during the initial period of acute illness, without loss of efficacy.