History, action and therapeutic used of Salvarsan, (Ehrlich-Hata "606")

The introduction of any drug which holds out some prospect of success in the treatment of spirillar and trypanosome diseases must, of necessity, attract great attention but no remedy has, up to the present, caused such a furore as Salvarsan. Although quinine, salicy - lates and tuberculin have all had great ovations they have not created such a universal enthusiasm as "606 ". Medical men have described its effects in *lowing terms and the lay press has contained some extraordinary statements about its curative properties.All these statements err on one point - the mention of the word cure. It cannot be too strongly insisted that we cannot promise that yet and the circulation of false powers will bring disappointment to some people and throw some discredit on the drug. On the other hand accounts of amaurosis after it are erroneous and they will tend to limit its use unfairly. Wechsel- mann, Ernest Lane, Pernet, Hutchinson and others have all tried to moderate the excessive enthusiasm which has arisen about it.In a third way false statements have been publish d. Some say it will supplant mercury and iodides but that is impossible. Cases are on record where these old and trusted remedies have acted and Salvarsan failed. There is no doubt however that it will limit their use.It marks the commencement of a new era in the treatment of parasitic diseases and, in time, it may become the parent of new substances which may have a still better action. At present it is doing excellent work and if we improve its technique and dosage or combine it with other substances we may, in time, wipe out the scourge of syphilis which has done so much evil since the middle ages

THE FORGOTTEN ORIGINS OF ANTIMICROBIAL RESISTANCE

The evolution and spread of resistance to antimicrobial drugs is currently viewed as a growing public concern, being ranked alongside other major threats such as climate change and terrorism. Interestingly, antimicrobial resistance is most often framed as a recent phenomenon, which results from the use and abuse of antibiotics in the clinic and husbandry. According to this view, the antimicrobial drugs used before the 1940s did not drive the emergence of resistance outside the laboratory and, therefore, antimicrobial resistance was not perceived as a clinical problem at the time. This dissertation challenges this view. By surveying major biomedical articles and textbooks on the treatment of syphilis with Salvarsan–one of the earliest antimicrobial drugs available in medicine–I show here that clinical antimicrobial resistance is older than we think, and that it motivated a reciprocal exchange of knowledge between the laboratory and the clinic, which have been claimed distant in the first decades of the 20th century. Importantly, the key primary sources used and analysed in this dissertation have hardly been cited by biomedical researchers and historians in their works on the history of antimicrobial resistance, despite being published in top-tier journals on syphilology and its treatment. This aspect begs the question: Why was the earlier history of drug resistance forgotten in these accounts? I argue that the historical amnesia about arsenic-resistant syphilis that I explore in this dissertation is consistent with what is known about the historical amnesia of biomedical knowledge more generally

The action and uses of Salvarsan

CHEMISTRY: Salvarsan is thedi-hydrochloride of dioxy-diamido-arseno-benzol. It is a pentavalent arsenical compound.SOLUTION FOR INJECTION: The di-sodium salt of Salvarsan was used for intravenous injections. It is dissolved in .85% normal saline, and is diluted so that every 40 c.c's of the solution contains .1 grammes of Salvarsan.DOSAGE: In practically every case .5 grammes Salvarsan was injected each time. As a rule not less than two injections were given at intervals of fourteen to twenty-one days. If necessary a further injection was administered, the indications being controlled by the Wassermann reaction.APPARATUS USED: The apparatus used was the one devised by Gibbard.DIAGNOSIS OF CASES: All cases treated had the diagnosis confirmed by either emonstrating the Treponema Pallidum in serum from the lesions, or by the performance of a Wassermann reaction. After treatment and progress of cases were controlled by the Wassermann reaction.PREPARATION OF PATIENT FOR THE INJECTION: Patients were taken into hospital the evening before the injection was to be given. They were given a mild purge and only a light meal was allowed on the morning of the injection. Before treatment all were carefully examined, special attention "being paid to the circulatory, nervous, digestive, and urinary systems.EFFECTS FOLLOWING THE INJECTION OF SALVARSAN: Rigors, a rise of temperature, headache, nausea and vomiting, and occasionally diarrhoea, follow the administration of the drug. The face and eyes "become congested and the pulse and respiration accelerated. Cyanosis was noted in a few cases. All these effects nave generally passed over "by the following day.Action on Skin and Mucous Membranes : Applied, in alkaline solution, to the unbroken skin or mucous membranes produced no effects. If abrasions were present slight irritation with hyperaemia was noted.ACTION ON THE GASTRO-INTESTINAL TRACK: Salvarsan is an irritant causing vomiting, and not infrequently diarrhoea with colicy pains.ACTION ON THE CIRCULATION: The cutaneous vessels of the face and chest are dilated by the injection of Salvarsan, and probably the vessels of the splanchnic area are similarly affected. On perfusing the vessels of a frog with the drug it causes them to dilate.The heart is accelerated in rate and may become slightly irregular and even dilate. In the frog the heart ceases in diastole, the ventricles being first to cease contracting. In the dog a similar effect is produced, the organ becoming engorged with blood .As a result of the weakening on the heart's action,and the dilatation of vessels,the blood pressure falls.ACTION ON THE WHITE BLOOD CORPUSCLES: A well marked leucocytosis is set up, due to the increase of the polymorphonuclear cells. The opsonic index is not affected.ACTION ON THE RED CELLS AND HAEMOGLOBIN: Salvarsan causes a rapid increase in the red cells and haemoglobin where these are deficient, the increase being more marked, at first in the haemoglobin.THE COAGULATION TIME of the blood is not affected.ACTION ON THE NERVOUS SYSTEM: Well marked headache follows the injection of the drug, due probably to its toxic action on the cells of the cortex. The sensory and motor nerves are not affected by the drug.ACTION ON THE URINARY SYSTEM: No bad effects were observed. In one case albumin in the urine disappeared after the injection of Salvarsan.ACTION ON METABOLISM: Rapid increase in weight and a great improvement in general condition, with a sense of well-being follows the injection of SalvarsanELIMINATION: Salvarsan is mainly excreted, in the urine, but it is also present in vomited matter and foeces.THERAPEUTIC EFFECTS: (1) IN SYPHILIS - Salvarsan causes a rapid disappearance of the lesions in all stages of the disease and accomplishes this in extremely short periods of time. The Wassermann reaction can, in all cases, be changed from a positive to a negative.A permanent cure is probably effected by the use of Salvarsan alone with supplementing it with Mercury.THERAPEUTIC EFFECTS: (2) IN LUPUS VULGARIS: Great benefit follows the administration of the drug in this conditionTHERAPEUTIC EFFECTS: (3) MALARIA: Good results follow its use in Malaria., especially the Benign Tertian form of the disease. It may succeed in accomplishing a cure where quinine has failed, this being especially marked in Malignant Malaria.THERAPEUTIC EFFECTS: (4) PIROPLASMO CANIS: The administration of Salvarsan to dogs suffering from this condition gave rise to extremely satisfactory résulté, complete cure followed the intravenous injection of the drug in the case of two Irish terrier pups treated in this way. A great field of usefulness in the treatment of this and the allied conditions of Texas Fever, and Bilary Colic in horses, is apparently open to the use of the drug

The history of general paralysis of the insane in Britain, 1830 to 1950

This thesis explores the history of ideas about, and responses to, general paralysis of the insane (GPI) - specifically in the context of the developing profession of psychiatry in Britain. It considers GPI as an objective disease entity whose subjective definition was nevertheless open to negotiation; for example, in deciding how central was overt insanity, or how GPI should be differentiated from the allied disease of tabes dorsalis. It explores how psychiatrists' interest in organicism and the science of medicine - and their attempts to raise the status of their specialty - both informed their understanding of GPI, and allowed them to promote it as a flagship disease for their profession. Nevertheless it draws attention to the gap between such claims and concrete practical advances which the disease fostered. The thesis considers changing causal explanations for GPI: first, in relation to the evolving image of the typical general paralytic patient; and second, in relation to the credence attached to different forms of causal evidence such as pathology, statistics, and laboratory medicine. It suggests how assessment of this evidence might have been informed both by professional aspirations and by pervasive cultural concerns such as fear of syphilis and degeneration theory. The thesis studies the use of malaria therapy to treat GPI in Britain, and uses this episode to explore a number of themes: early twentieth century ethical attitudes to heroic treatments; perceptions of 'cure'; and the change in emphasis from asylum care to community care. Finally, it considers ideas about the epidemiological history of the illness - from early twentieth-century theories about the evolution of infections, to Edward Hare's hypothesis of a neurotropic epidemic; and considers how the views of disease as objective entity, and disease as cultural construct, might be reconciled in the context of GPI