Background:Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I–II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown.Methods:Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20.Results:Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS−), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS− patients receiving at least four doses at 320 IU m−2 was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024.Conclusion:ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression.

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In discussions of the composition of human milk and of modifications of cow's milk, much stress is laid on the absolute and relative proportions of fats, carbohydrates and protein, but, as a rule, no mention is made of the concentration of the mineral constituents. As an example, we may cite the fact that in many clinics the most premature infant is given mixtures of whey, which may provide certain advantages in regard to the quality of the protein, but which contain 300 per cent. more chlorids than does human milk. A similar relation exists in connection with several of the other inorganic constituents.This practice is, of course, based on the assumption that an excess of inorganic material is present even in human milk, and that this excess is not injurious, an assumption not based on experimental evidence. Theoretically, it is, of course, perfectly conceivable that such an excess of salts may not only increase the work of the kidneys to a dangerous degree, but may even induce intestinal disturbances. Stimulated by recent work which has demonstrated the importance of the mineral elements of the diet, we began about one year ago a study of the mineral constituents of human milk and of the various modifications of cow's milk ordinarily used in infant feeding. In this paper, which is the first of a series dealing with this subject, we shall consider only findings on the chlorids of human milk. METHOD OF ANALYSISBefore attempting the collection of data, it was first necessary to find an analytical method by means of which it would be possible to obtain accurate results with a moderate outlay of time, and with relatively small amounts of material. Most of the milk chlorid deter¬ minations recorded in the literature were made either by gravimetric methods, usually from the weight of silver chlorid, or by the Volhard titration. In either case, a considerable volume of milk had to be evaporated to dryness, ashed in a platinum dish at low heat with the

Scattered through the literature of basal metabolism there are isolated reports of the metabolism findings of premature infants, but up to date no series of cases has been studied consistently showing the characteristics of this type of infant.We are presenting in this communication the basal metabolism of seven of the twenty-two premature infants studied by us during the past year and a half, in its relation to the caloric intake and the weight curves.A search of the literature gives much data in regard to the caloric intake and requirements of premature infants but in no instance have the caloric intake and the basal metabolism been recorded for the same infant.The source of the material used was the Boston Lying-In Hospital and the Children's Department of the Massachusetts General Hospital. The subjects were all examined physically, were all organically sound, but had the characteristic appearance of premature infants, and, so far as we were able to determine, were prematurely born from one to two months. These premature infants had high pulse rates, unstable temperatures, and were at first too weak to nurse the breast. They were consequently either fed by a Breck feeder or by tube. Breast milk was given whenever possible, but, as the supply was not unlimited, it was often necessary to supplement dilute cow's milk formulas.