736

More experience is needed to evaluate streptokinase-heparintherapy. We wonder whether the lysis is rapid and completeenough to prevent ischxmic necrosis of the involved glomeruli.

L. MONNENSE. SCHRETLEN.

Department of Pædiatrics,St. Radboud Ziekenhuis,

Nijmegen, Holland.

PHENYLBUTAZONE FOR PROLAPSED DISCS?

SIR,-Several workers 1 have suggested that phenylbutazoneis effective in the treatment of prolapsed intervertebral discs.The rationale for its use is based on the observation 2 thatinflammation, rather than direct pressure of disc material on thenerve-root, is often responsible for the clinical picture. Previousstudies have not been double-blind, and we should like toreport on such a trial.

All patients between 18 and 53 years of age presenting withpain from the low back or buttock, radiating down the back ofthe leg to at least the heel, and either pain on straight-leg-raising referred to the contralateral thigh or back, muscularweakness, or sciatic-nerve tenderness were admitted to hospital.All patients with X-ray evidence of disease of the lumbosacralspine, a history of prior back surgery, or upper gastrointestinaldisease were excluded. As an adjunct to our usual conservativemethods of treating these patients for 3 full weeks before

myelogram and surgical intervention are considered, phenyl-butazone (in 100 mg. capsules) or a placebo were administered.They were given six a day for 2 days, then three a day for8 days in double-blind fashion. Two of the original twenty-fivepatients in the study had to be excluded. One who receiveddrug was later found to have metastatic carcinoma. Another,on placebo, developed tinnitus. We were thus left with twenty-three patients-twelve drug-treated and eleven controls.Twelve underwent laminectomy-six drug-treated and sixcontrols.

In order to compare the effect of the drug on the elevenpatients who did not require surgery (six drug-treated and fivecontrols), we summed each subject’s clinical response for thelast 3 days of treatment and subtracted that from the sum ofhis responses for the first 3 days of treatment. This was donefor each of two subjective symptoms (sciatica at rest and overalldiscomfort) and for each of four objective signs (painfulstraight-leg raising, pain contralaterally on straight-leg raising,motor weakness, and popliteal compression). These featureswere graded on a scale of 0-3: absent, slight, moderate, andsevere. (Straight-leg raising was scored in 30° increments.) Wepersonally made all the measurements in order to lessen theirrelative subjectiveness. Since the return of sensory and reflexdeficits, and the amount of pain medication consumed wereunrelated to the clinical course, we did not use these indices forrating purposes.

Because the samples were small and most of the distributionsdid not meet the assumption of normality, statistical tests forsignificance were made by the Mann-Whitney U test ratherthan by the more familiar t test for uncorrelated means. (TheMann-Whitney U test is a nonparametric statistic, of con-siderable analytical power, which does not assume normality ofdistribution.)The drug-treated group’ showed a statistically significant

improvement in motor weakness (at the 0-05 confidence level)and in painful straight-leg raising (at the 0-10 confidence level).Sciatica at rest, the sum of all objective signs combined, andall objective plus subjective ratings combined, fell just short ofthe 0-10 level of significance.

White-blood-cell counts, differential counts, haematocrits,and stool guaiac tests were performed on admission and after2 and 7 days. Except for transient slight melxna in one patientand mild epigastic burning in two others, relieved by antacids,there were no demonstrable side-effects from the phenyl-butazone.The high proportion of patients operated on was probably

1. Steer, C. Lancet, 1956, i, 966. Gillhespy, R. O. ibid. p. 1069; ibid. 1959,i, 522. Strandberg, B. Acta rheum. scand. 1965, suppl. 10.

2. Hirsch, C. J. Bone Jt Surg. 1956, 38A, 242.

a result of the strict criteria for inclusion in the study. Althoughthe proportion of patients requiring laminectomy was notdecreased by phenylbutazone, both subjective and objectivefindings improved more rapidly with the drug. However, theinability of phenylbutazone to significantly alter the proportionof patients requiring surgical intervention would seem to

militate against the use of this drug for this disease. Thevariance of these findings with previous reports may perhaps beexplained by the strictness of our experimental design.

Phenylbutazone and placebo were both kindly supplied by theGeigy Pharmaceutical Corporation, Ardsley, New York. This studywas carried out at the Orthopedic Service, Andrews Air Force BaseHospital, Washington, D.C.

ERIC L. RADIN.

Department of Orthopedic Surgery,Massachusetts General Hospital,Boston, Massachusetts 02114.

RICHARD S. BRYAN.

Section of Orthopedic Surgery,Mayo Clinic Foundation,

Rochester, Minnesota 55901.

TOXICITY OF A TRIMER OF MALONONITRILESIR,-Malononitrile has sometimes been considered to be

non-toxic, though evidence indicates that it is as toxic as cyanideon a molecule-for-molecule basis. We now have data whichindicate that cyanide is also released from a trimer ofmalononi-trile, U-9189 (1,1,3-tricyano-2-amino-l-propene, Upjohn Co.,Kalamazoo, Michigan). This compound has been used bothexperimentally and in clinical trials in attempts to improvelearning. This compound or a placebo was given twice daily to

Effect of U-9189, placebo, sex, smoking, and (?) aspirin on excretionof potassium thiocyanate.

educable retarded children, 12-16 years of age, in a dosage of150 mg. twice a day in a double-blind study. Thiocyanate, adetoxification product of cyanide, was measured in urine

samples obtained from the children during the drug-studyperiod. (Twenty-four-hour-urine collections were not feasibleunder the conditions of the experiment and blood-samplescould not be obtained without disturbing the concurrent

psychological testing.) The urine specimens were analysedby a modification of Barker’s method 2 for thiocyanate. It wasnot possible to obtain a colourless filtrate urine by addingtrichloroacetic acid (T.C.A.); only after Lloyd’s reagent plusT.C.A. was added were most of the filtrates colourless. Tocorrect for any colour in the filtrates each unknown was read

1. Henderson, R. Science, N. Y. 1968, 159, 482.2. Barker, M. H. J. Am. med. Ass. 1936, 106, 762.