This brief history of the use of extracts of Colchicum autumnale in the treatment of gout had its origin in some research relative to the metabolism and mode of action of colchicine. It was interesting to review this history in order to develop a background, and thus to learn what ancient authorities and later observers knew about this drug. We shall review the evidence for the identity of certain plants thought by many investigators to be identical with our modern Colchicum autumnale, and which were described by early writers as poisons and later recommended in the treatment of gout; re-emphasize knowledge which has been more or less forgotten but which could be of experimental and practical usefulness to-day; delineate the fluctuations of popularity of colchicum as a treatment for gout during the past 1,500 years; and briefly mention the history of its uses in other fields of research. At the present time colchicine and its derivatives, as well as other mitotic-arresting drugs, are of considerable importance in the field of cancer research. More thoroughly established, however, is the role of colchicine in the treatment of acute attacks of gout, and it is this latter role that concerns us most here.In the preparation of this study we have received invaluable assistance from Professor
Malignant hyperthermia (MH) is a rare autosomally dominantly hereditary and potentially life-threatening disease. The prevalence of the genetic MH predisposition is estimated as 1:10,000 to 1:20,000. In Germany no data on the regional distribution are available. Therefore, the purpose of this investigation is to summarise and present the epidemiological data of all German MH laboratories. Nine German hospitals offer the specific in vitro contracture test to diagnose the MH predisposition. All German MH laboratories carry out the examination in accordance with the standardised protocol of the European Malignant Hyperthermia Group. The laboratories were asked to provide the number of all patients investigated, excluding those suffering from other neuromuscular diseases, separated according to diagnostic groups and their places of residence, the number of the identified MH-families as well as the number of the clinically suspected and investigated MH cases with their places of residence. Eight MH laboratories provided the requested data. Until September 1997 a total of 2620 patients were investigated. In 865 patients (34%) MH suspicion was confirmed (diagnosis: MHS). 1494 patients (56%) were released by investigation from MH-suspicion (diagnosis: MHN). In 261 patients (10%) the MH-predisposition remained unsolved (diagnosis: MHE). 580 MH families were identified. Among 2620 patients 757 were clinically suspected MH cases. 35% of these suspected MH cases were classified as MHS, 10% as MHE and 55% as MHN. The documentation of the patients places of residence classified as MHS and MHE into a map of Germany demonstrates an exhaustive distribution with an increased regional prevalence in the areas of the MH laboratories. This concentration in the area of the MH laboratories becomes even more evident, when the places of residence of the MH suspected cases are demonstrated. In conclusion, the distribution of the MH predisposition is uniform and exhaustive in Germany. The presented regional concentration of clinically suspected MH cases among the MH laboratories is mainly interpreted as an expression of effective regional education and information. Considering the overall incidence of the MH predisposition as described above only 15-20% of the MH patients have so far been identified. The MH laboratories have already released about 10,000 patients from the suspicion of MH predisposition. A preliminary prevalence of at least 1:60,000 to 1:80,000 in Germany can be estimated according to the presented data.
REVIEW of our knowledge of colchicine as it pertains to its effects A in relieving the symptoms of acute gout is useful for at least two reasons.One is that further study of the disorganizing effects of colchicine on the mitotic spindle, probably composed of a fibrous protein with a sulfhydryl riidical, may lead us to the identification of a possible intermediary sulxtance in purine synthesis responsible for the acute gouty attack. Secondly, with the availability of many new colchicine analdgs, there is hope that a more eitective, less toxic. anti-gout drug than colchicine may be discovered.The literature' pretaining to colchicum, the crude extract. and colchicine, one of its purified extracted ingredients, is extremely voluminous, in spite of the fact that comprehensive research in this field begm as late as 1934, with the observation by A. P. D~istiii, Sr.2 that colchicine had B unique effect on mitosis, poisoning the spindle at the metaphase of cell division. We now know that as little as one part in a billion can produce this effect.Mitotic poisons had been studied for a long time, iictually since Hertwig ( 1887),3 who worked with narcotics. A. P. Dustin, Sr. had experimented with many chemicals before his attention was directed to colchicine. Since 1934, colchicine has been used to an enormous extent in such diverse fields as agriculture, genetics, cell physiology, the study of birth malformations and cancer research. Before its demonstration as a mitotic poison, its only usefulness was in the treatment of gout, based on empirical observation dating hack to the (lawn of history. Those interested in the absorbing historv of colchicum may read the author's paper." THE NATURALLY OCC;URRING COMPOUNDSAlthough the exact formula of colchicine, one of the purified ingredients of colchicum, is now well established, its actual synthesis in the laboratory has not been accomplished. We still must obtain our materials from the natural source. There are 64 varieties of the plant colchicum (B. Stefanoff, 1928),6 all members of the lily family. At least 30 cwntain colchicum. In the western world, the source is mainly the corm m d seed of Colclzicunr crzrtunrrde, a plant found growing wild in the hlediterranean basin. Many other varieties are found further west, to the foothills ok the Himalaya Mounatins.Briefly, colchicine is extracted from the corm and seed with alcohol and water, and then from this solution with chloroform. The latter is evaporated off, yielding amorphous colchicine, which can be crystallized from solution in ethyl acetate. Chromatographic purification is then accomplished by the method of Ashley and Harris (1944).'; This yields practically pure colchicine. Santavy and his co-workers have extracted iit lwst nine other analogs naturally present in the plant itself. From these basic natural compounds a host of syntheticallv derived analogs have been developed, mainly for experimental 18
HE CENTRAL THEME of this summary of current treatment of osteo-T arthritis is that, while the etiology is incompletely understood, and while some recognized factors are beyond our control others, and most especially loss of stability and coordination of joint mobility, are potent factors often amenable to therapy. The loss of stability results particularly in shearing trauma which upsets the balance between normal cartilage growth and degeneration. This loss of stability, with or without externally applied super- However, to say that the "cause" is unknown and therefore the effective management nil, is to deny important facts obvious to many observers, particularly those sensitized by an orthopedic awareness, and this includes more and more medical men with a particular interest in the problems of arthritis and rheumatism.
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