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indications wilson s disease two types of patients require treatment for wilson s disease 1 the symptomatic and 2 the asymptomatic in whom it can be assumed the disease will develop in the future if the patient is not treated diagnosis suspected on the basis of family or individual history physical examination or a low serum concentration of ceruloplasmin is confirmed by the demonstration of kayser fleischer rings or particularly in the asymptomatic patient by the quantitative demonstration in a liver biopsy specimen of a concentration of copper in excess of 25 mcg g dry weight treatment has two objectives 1 to minimize dietary intake and absorption of copper 2 to promote excretion of copper deposited in tissues the first objective is attained by a daily diet that contains no more than one or two milligrams of copper such a diet should exclude most importantly chocolate nuts shellfish mushrooms liver molasses broccoli and cereals enriched with copper and be composed to as great an extent as possible of foods with a low copper content distilled or demineralized water should be used if the patient s drinking water contains more than 1 mg of copper per liter for the second objective a copper chelating agent is used in symptomatic patients this treatment usually produces marked neurologic improvement fading of kayser fleischer rings and gradual amelioration of hepatic dysfunction and psychic disturbances clinical experience to date suggests that life is prolonged with the above regimen noticeable improvement may not occur for one to three months occasionally neurologic symptoms become worse during initiation of therapy with depen despite this the drug should not be discontinued permanently although temporary interruption may result in clinical improvement of the neurological symptoms it carries an increased risk of developing a sensitivity reaction upon resumption of therapy see warnings for quantitative test for serum ceruloplasmin see morell a g windsor j sternlieb i scheinberg i h measurement of the concentration of ceruloplasmin in serum by determination of its oxidase activity in laboratory diagnosis of liver disease f w sunderman f w sunderman jr eds st louis warren h green inc 1968 pp 193 195 treatment of asymptomatic patients has been carried out for over ten years symptoms and signs of the disease appear to be prevented indefinitely if daily treatment with depen can be continued cystinuria arginine lysine ornithine and cysteine are soluble substances readily excreted there is no apparent pathology connected with their excretion in excessive quantities cystine however is so slightly soluble at the usual range of urinary ph that it is not excreted readily and so crystallizes and forms stones in the urinary tract stone formation is the only known pathology in cystinuria normal daily output of cystine is 4 to 8 mg in cystinuria output is greatly increased and may exceed 1 g day at 5 to 6 mg day stone formation is almost certain when it is more than 3 mg day treatment is indicated conventional treatment is directed at keeping urinary cystine diluted enough to prevent stone formation keeping the urine alkaline enough to dissolve as much cystine as possible and minimizing cystine production by a diet low in methionine the major dietary precursor of cystine patients must drink enough fluid to keep urine specific gravity below 1 1 take enough alkali to keep urinary ph at 7 5 to 8 and maintain a diet low in methionine this diet is not recommended in growing children and probably is contraindicated in pregnancy because of its low protein content see precautions when these measures are inadequate to control recurrent stone formation depen may be used as additional therapy when patients refuse to adhere to conventional treatment depen may be a useful substitute it is capable of keeping cystine excretion to near normal values thereby hindering stone formation and the serious consequences of pyelonephritis and impaired renal function that develop in some patients bartter and colleagues depict the process by which penicillamine interacts with cystine to form penicillamine cysteine mixed disulfide as in this process it is assumed that the deprotonated form of penicillamine ps is the active factor in bringing about the disulfide interchange rheumatoid arthritis precautions
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