YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==ELEPHANTIASIS AND LYMPHEDEMA== 1 AUTHOR Casley-Smith JR AUTHOR Wang CT AUTHOR Casley-Smith JR AUTHOR Zi-Hai C TITLE Treatment of filarial lymphedema and elephantiasis with 5,6-benzo-alpha-pyrone (coumarin) SOURCE Br. Med. J.; VOL 307 ISS Oct 23 1993, P1037-1041, (REF 28) ABSTRACT IPA COPYRIGHT: ASHP The therapy of filarial lymphedema and elephantiasis is reported in 104 adult patients, 64 of whom were given 200 mg of coumarin (5,6-benzo-alpha-pyrone) twice daily for 367 days and 40 were given placebo. Coumarin reduced edema for all grades of lymphedema during the yr of treatment and the follow-up yr. At the end of the trial the total reduction in edema was 100%, 95%, and 45%, for grades 1, 2, and 3-5 lymphedema, respectively. Symptoms and complications were considerably reduced, including attacks of secondary acute inflammation, while side effects were minor and disappeared after 1 month. In the placebo group there were no changes in the severity of lymphedema. It was concluded that coumarin reduces the edema and many symptoms of filarial lymphedema and elephantiasis. It has few side effects, and its relatively slow action makes it ideal for use without compression garments. 2 AUTHOR Casley-Smith JR AUTHOR Jamal S AUTHOR Casley-Smith J TITLE Reduction of filaritic lymphoedema and elephantiasis by 5,6 benzo-alpha-pyrone (coumarin), and the effects of diethylcarbamazine (DEC). SOURCE Ann Trop Med Parasitol; VOL 87, ISS 3, 1993, P247-58 ABSTRACT Chronic filaritic lymphoedema and elephantiasis, in India, were treated orally with 5,6 benzo-alpha-pyrone (56 BaP; 1,2 benzo-alpha-pyrone; coumarin) in a double-blind, randomized, matched-group trial. Each group finally contained 40-55 patients. Patients were observed for about 2 years (ranging from 6 to 45 months, with 75% completing the 2 years). The 56 BaP slowly, but very significantly (P < 0.0001), reduced all grades of lymphoedema and elephantiasis. Two thirds of the oedema was lost by grade 2 over 2 years. Grades 3 to 5 were reduced by a fifty over that time. The greater the initial oedema, the greater was its rate of resolution. A slowly worsening condition thus became a slowly improving one. Slowness has its advantages: compression stockings, that are impractical in hot, wet or dirty conditions, are not necessary. The slowly remodelling fibrous tissue, while lessening in amount, is still able to hold the tissues together. The 56 BaP considerably improved many symptoms and complications, particularly bursting-pains, inflammation and ulcers. It is cheap and of very low toxicity. Diethylcarbamazine (DEC) was studied with and without 56 BaP. DEC alone gave some reduction of the oedema, but this was much smaller than that with 56 BaP. It considerably worsened the reductions by 56 BaP, while 56 Bap slightly improved those by DEC and reduced the fever caused by DEC. Together, they reduced feelings of swelling and bursting-pain, fungal infections, lymphangitis and lymphadenitis more than when used alone. 3 AUTHOR Casley-Smith JR AUTHOR Casley-Smith JR TITLE Modern treatment of lymphoedema. II. The benzopyrones. SOURCE Australas J Dermatol; VOL 33, ISS 2, 1992, P69-74 (REF: 9) ABSTRACT The benzo-pyrones reduce all high-protein oedemas, including lymphoedema and elephantiasis, by increasing the numbers of macrophages and their normal proteolysis. Thus they remove the excess protein, and thereby the oedema which is caused by it. They also remove the stimulus it provides for chronic inflammation and fibrosis, and its action as a culture medium for bacteria. Coumarin (5,6 benzo-[alpha]-pyrone, 56 BaP) and oxerutins (HR, O(beta-hydroxy-ethyl)-rutosides) have been used in many clinical trials on a variety of high-protein oedemas. Four such trials are summarised here: on lymphoedema and elephantiasis (from many causes in Australia, and filaritic in India and China). The drugs reduced these much more slowly than adequate physical therapy, but they did reduce them. About half the excess volume was removed over six months in the Australian trials. In India and China similar rates were achieved with lymphoedema, but elephantiasis reduced at a slower rate. The benzo-pyrones convert a slowly worsening condition into a slowly improving one. No compression garments are necessary. In addition, the drugs considerably reduce the number of attacks of secondary acute infection, reduce the deformities of elephantiasis and considerably improve the patients' comfort and mobility. They may be taken orally, or applied topically, have very low toxicities and only few, minor side-effects. They are useful in many other forms of high-protein oedema, and improve the results of physical therapy for lymphoedema. 6 AUTHOR Casley-Smith JR AUTHOR Casley-Smith JR TITLE The pathophysiology of lymphedema and the action of benzo-pyrones in reducing it. SOURCE Lymphology; VOL 21, ISS 3, 1988, P190-4 (REF: 13) ABSTRACT The pathogenesis of lymphedema is briefly reviewed. Swelling secondary to lymphostasis shares the common deleterious effects of other edemas, especially those of chronic high protein edema, namely chronic inflammation with excess tissue fibrosis. Benzo-pyrones are the only known drugs which reduce the excess protein in the tissues with high protein edema including lymphedema. Once excess tissue protein is resorbed, edema subsides and the fibrosis slowly resolves by remodeling. Two of these benzo-pyrone drugs have been shown to reduce postmastectomy and primary lymphedema in randomized, double-blind, cross-over, placebo-controlled trials. One of these drugs (which is also inexpensive) has also been shown to reduce filaritic lymphedema and elephantiasis in a similar trial in India. The bigger the leg initially, the more rapid is the reduction. In this extreme condition about a 20% lessening of the excess volume occurs each year. The benzo-pyrones do not work rapidly, but they do convert a rapidly worsening condition into a slowly improving one. In addition, they have extremely low toxicity and are effective orally. They also seem to reduce the incidence of secondary acute inflammation.