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D-penicillamine was administered to 15 patients with rheumatoid arthritis. A fall in the titer of rheumatoid factor was demonstrated in all patients. The sedimentation rate decreased in most patients. There was no consistent alteration in immunoglobulins A, G or M or in lymphocyte transformation attributable to penicillamine. Ceruloplasmin serum levels were lowered significantly in 7 patients. Clinical improvement in the arthritis resulted in 10 patients.Penicillamine has been found useful in the treatment of such diverse conditions as Wilson's disease, macroglobulinemia of Waldenstrom, certain heavy metal intoxications, cystinuria, autoimmune hemolytic anemia and cold agglutinin disease. Its versatile effects on parameters known to be altered in rheumatoid arthritis-namely, serum macroglobulins (1-3) , serum copper (4-5) and sulfhydryl levels (6-7), pyridoxine metabolism (8) and collagen (9) -suggest that its investigation might prove fruitful. Jaffe has published several papers (1, 3, 10, 11) on the administration of penicillamine to patients with rheumatoid arthritis. He has demonstrated clinical improvement as well as certain changes in laboratory parameters, especially a fall in the titer of rheumatoid factor and erythrocyte sedimentation rate. Our experience with D-penicillamine in the treatment of rheumatoid arthritis is presented here. MATERIALS AND METHODSFifteen patients with rheumatoid arthritis (R.4) , hy the criteria of the American Rheumatism Association (ARA) (12), were treated with D-penicillamine. T e n were women; all were over age 40, 4 were over 60. All had had the R.4 for more than 4 years. Table 1 gives their initial clinical status.Gradually increasing doses of penicillamine, beginning with 0.5 g/day and reaching 1 g/day in about 6 weeks. were prescribed. T h e daily maintenance close eventually reached 1.0 in 6 patients, 1.5 in 4 patients and 2.0 g in 5 patients. Of the 5 patients who received 2 g/tlay, 4 received this close for more than 4 months. T h e drug was stopped after 12-18 months of treatment; 1 patient did not return after heing treated for 7 months.Previously administered medications, which included salicylates, other analgesics, oxyphenbuta-

Gliosarcoma is a subset of glioblastoma with glial and mesenchymal components. True secondary gliosarcomas (i.e. progressing from lower-grade precursors) in the absence of radiation therapy are very rare. We report the unique case of a 61-year-old male who developed a fibrillary astrocytoma (WHO grade II). In the absence of adjuvant therapy the tumor recurred 3 years later as a gliosarcoma comprising an infiltrating glial component and a curious, early high-grade sarcomatous component surrounding intratumoral vessels. DNA was extracted from formalin fixed paraffin-embedded tissues from the precursor low-grade glioma and from the glioma and sarcomatous components at progression. Samples were hybridized separately to a 300 k Illumina SNP array. IDH1(R132H) mutant protein immunohistochemistry was positive in all tissue components. Alterations identified in all samples included dup(1)(q21q41), del(1)(q41qter), del(2)(q31.1), del(2)(q36.3qter), del(4)(q35.1qter), dup(7)(q22.2q36.3), del(7)(q36.3qter), del(9)(p21.3pter), dup(10)(p13pter), del(10) (q26.13q26.3), dup(17) (q12qter), and copy neutral LOH(20)(p11.23p11.21). The recurrent tumor had additional alterations, including del(3)(p21.31q13.31), del(18) (q21.2qter), and a homozygous del(9)(p21.3)(CDKN2A locus) and the sarcoma component had, in addition, del(4)(p14pter), del(6)(q12qter), del(11)(q24.3qter), and del(16)(p11.2pter). In conclusion, unique copy number alterations were identified during tumor progression from a low-grade glioma to gliosarcoma. A subset of alterations developed specifically in the sarcomatous component.

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