On Aneurysmal Rupture and Rerupture.

A warning leak is a curious phenomenon attributed to cerebral aneurysms. Once the leak occurs, it has been postulated it could lead to a more catastrophic rebleeding. The designation "warning leak" trickled into neurosurgery vocabulary as early as the 1950s. The phenomenon has been poorly understood and characterized, but its presence spurs emergency physicians and neurointensivists to take action to secure the aneurysm. Rapid treatment of a recently discovered aneurysm is now commonplace, but it has not always been so. Antifibrinolytic agents spawned particular interest in the late 1970s, when many neurosurgeons postponed surgery after a recent hemorrhage. This historical vignette reviews the early views on aneurysmal rupture, rerupture, and the role of fibrinolysis.

[On the history of vitamin K, dicoumarol and warfarin]. / Pionerer bag vitamin K, dikumarol og warfarin.

The history of the discovery and development of vitamin K and its antagonists, the oral anticoagulants dicoumarol and warfarin, are fascinating, triumphant landmarks in the annals of medicine. Vitamin K was found by Carl Peter Henrik Dam and Fritz Schønheyder from the University of Copenhagen. The discovery was initiated by Dam, by a lucky choice of chicks in the dissertation of sterol metabolism, since the vitamin is not formed by intestinal bacteria in these animals. In these experiments the lack of an unknown factor in the synthetic diet caused internal bleeding similar to that found in scurvy, but the bleeding was not reversed by vitamin C and it could not be explained by the lack of classical vitamins. In 1935 the unknown antihaemorrhagic factor was named vitamin K and a few months later the phenomenon was also observed by H.J. Almquist and E.L.R. Stokstad in Berkeley. The activity of the factor was determined by bioassay in different extracts of green vegetables and alfalfa by Dam and Schønheyder. Vitamin K was isolated in 1939 by Dam and Paul Karrer in Zurich and the structure was determined by Edward Adelbert Doisy. Dam and Doisy were awarded the Nobel Prize in 1943. A dramatic story starts the discovery of dicoumarol. In the 1920s cattle in Canada began dying of internal bleeding with no obvious precipitating cause. Frank W. Schofield, a veterinary pathologist in Alberta, found that the mysterious disease was connected to the consumption of spoiled sweet clover hay and noted a prolonged clotting time. Ten years after a farmer traveled in a blizzard with his dead cow and a milk can of the unclotted blood to the University of Wisconsin. Only the door to the biochemical department of Karl Paul Link was open. This event started the isolation of the anticoagulant agent dicou- marol which was formed by microbial induced oxidation of coumarin in the mouldy sweet clover hay. More than hundred dicoumarol-like anticoagulants were synthesized by Link and his co-workers. A potent hemorrhagic agent named warfarin was first used as an effective rat poison. However, warfarin became the drug of choice and the break- through in the treatment of thromboembolic diseases. Today new oral anticoagulants are competing with warfarin.

Traumatic hyphema: a critical review of the scientifically catastrophic history of steroid treatment therefore; and A report of 24 additional cases with no rebleeding after treatment with the Yasuna systemic steroid, no touch PLUS protocol.

PURPOSE: To establish a detailed history of steroid therapy administered either systemically or topically for traumatic hyphema (TH) over the past 40 years. To this literature, we report and add another 24 TH cases treated with the Yasuna systemic steroid No Touch PLUS protocol. METHODS: Review of all reports in Medline since its inception in 1966 and such reports not in Medline but retrievable by successive reference and various alternate sources. Retrospective review of charts of all cases of TH at the University of Florida from 1980-1987. Of 135 cases so retrieved, 24 were found who had received this treatment protocol properly. (Ethical, moral and liability aspects prohibited a formal comparative study of a no medical treatment control group since this is unconscionable and abusive at the present state of knowledge.) RESULTS: The historical review revealed that there is general ignorance of the salutary effect of both topical and systemic steroids in reducing the rebleed rate in TH. This is so marked that at least five experiments reported in the literature are invalidated to a variable degree because all patients, in both the experimental and control groups, had received topical steroids. Further, that the remarkable reduction in the rebleed rates for control groups of theoretically medically untreated TH, from the vicinity of 25% or more to the vicinity of 10-15% appears to be due primarily, if not solely, to this now ubiquitous administration of topical steroids in TH. In addition, in retrospect, there are also a remarkable number (at least 5) of major statistical errors in this literature and another 6 studies of outpatients in which compliance with therapy as outpatients is not even considered. Therefore at least 16 (57%) of the 28 papers reviewed have serious flaws and doubtful or uncertain results or conclusions. Of the 9 papers which lead one to wrongful conclusions, 5 are prejudicial against systemic steroid treatment (and 2 against systemic ACA treatment, and 2 against systemic TXA treatment). All but one of the nine are, as a corollary, prejudicial in favor of non medical treatment of TH. In our 24 cases studied, none suffered a rebleeding episode. CONCLUSIONS: The "continuing controversy" about medical treatment of TH is the direct result of poor science and poor scientific methods in clinical trials. Because no method has yet been devised to determine which traumatic hyphemas will rebleed, but preventing rebleeding is about all that we can do maximize the outcome, we recommend that all patients with TH receive the Yasuna systemic steroids no touch and/or PLUS protocol in addition to current conventional treatment (bed rest, hospitalization for all patients under 18 years of age)

Oral vitamin K1: an option to reduce warfarin's activity.

OBJECTIVE: To report 6 patients taking oral vitamin K1 (phytonadione) to reduce warfarin's activity. CASE SUMMARY: Six patient cases are summarized in which oral vitamin K1 was used to reduce the international normalized ratio (INR) in patients at risk of bleeding. DISCUSSION: The use of oral vitamin K1 to antagonize warfarin's effects is discussed, as well as the benefits of oral vitamin K1 administration and the disadvantages of parenteral vitamin K1 administration. In addition, an extensive literature review of the discovery and clinical development of warfarin and vitamin K1 is described. CONCLUSIONS: In patients receiving warfarin therapy who have an increased INR and are at risk of bleeding, oral vitamin K1 therapy may be safer, less painful, and more cost-effective than the traditional parenteral route of administration.